Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.

In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.

“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”

Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.

“If claims are going down, I don’t understand why premium payments are going up,” she said.

Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.

Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.

Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.

According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.

The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
 

Cases plummet during pandemic

During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.

“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”

The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.

“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”

In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.

But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.

“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
 

High-dollar verdicts pave expensive path

The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.

“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”

In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.  

Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.

“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”

High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.

“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
 

What does 2022 have in store?

Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.

Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.

Such delayed claims may end up costing more because of social inflation, said Mr. Burns.

“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”

Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.

“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”

As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.

“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”

For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.

“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”

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

Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.

In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.

“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”

Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.

“If claims are going down, I don’t understand why premium payments are going up,” she said.

Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.

Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.

Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.

According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.

The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
 

Cases plummet during pandemic

During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.

“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”

The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.

“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”

In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.

But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.

“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
 

High-dollar verdicts pave expensive path

The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.

“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”

In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.  

Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.

“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”

High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.

“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
 

What does 2022 have in store?

Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.

Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.

Such delayed claims may end up costing more because of social inflation, said Mr. Burns.

“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”

Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.

“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”

As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.

“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”

For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.

“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”

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

Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.

In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.

“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”

Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.

“If claims are going down, I don’t understand why premium payments are going up,” she said.

Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.

Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.

Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.

According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.

The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
 

Cases plummet during pandemic

During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.

“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”

The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.

“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”

In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.

But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.

“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
 

High-dollar verdicts pave expensive path

The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.

“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”

In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.  

Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.

“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”

High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.

“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
 

What does 2022 have in store?

Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.

Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.

Such delayed claims may end up costing more because of social inflation, said Mr. Burns.

“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”

Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.

“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”

As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.

“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”

For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.

“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”

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

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

The study was published online in the American Journal of Geriatric Psychiatry.
 

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

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

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

The study was published online in the American Journal of Geriatric Psychiatry.
 

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

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

Opioid use in the elderly is associated with an almost 40% increased risk of dementia in new findings that suggest exposure to these drugs may be another modifiable risk factor for dementia.

“Clinicians and others may want to consider that opioid exposure in those aged 75-80 increases dementia risk, and to balance the potential benefits of opioid use in old age with adverse side effects,” said Stephen Z. Levine, PhD, professor, department of community mental health, University of Haifa (Israel).

The study was published online in the American Journal of Geriatric Psychiatry.
 

Widespread use

Evidence points to a relatively high rate of opioid prescriptions among older adults. A Morbidity and Mortality Weekly Report noted 19.2% of the U.S. adult population filled an opioid prescription in 2018, with the rate in those over 65 double that of adults aged 20-24 years (25% vs. 11.2%).

Disorders and illnesses for which opioids might be prescribed, including cancer and some pain conditions, “are far more prevalent in old age than at a younger age,” said Dr. Levine.

This high rate of opioid use underscores the need to consider the risks of opioid use in old age, said Dr. Levine. “Unfortunately, studies of the association between opioid use and dementia risk in old age are few, and their results are inconsistent.”

The study included 91,307 Israeli citizens aged 60 and over without dementia who were enrolled in the Meuhedet Healthcare Services, a nonprofit health maintenance organization (HMO) serving 14% of the country’s population. Meuhedet has maintained an up-to-date dementia registry since 2002.

The average age of the study sample was 68.29 years at the start of the study (in 2012).

In Israel, opioids are prescribed for a 30-day period. In this study, opioid exposure was defined as opioid medication fills covering 60 days (or two prescriptions) within a 120-day interval.

The primary outcome was incident dementia during follow-up from Jan. 1, 2013 to Oct. 30, 2017. The analysis controlled for a number of factors, including age, sex, smoking status, health conditions such as arthritis, depression, diabetes, osteoporosis, cognitive decline, vitamin deficiencies, cancer, cardiovascular conditions, and hospitalizations for falls.

Researchers also accounted for the competing risk of mortality.

During the study, 3.1% of subjects were exposed to opioids at a mean age of 73.94 years, and 5.8% of subjects developed dementia at an average age of 78.07 years.
 

Increased dementia risk

The risk of incident dementia was significantly increased in those exposed to opioids versus unexposed individuals in the 75- to 80-year age group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.92; z statistic = 2.02; P < .05).

The authors noted the effect size for opioid exposure in this elderly age group is like other potentially modifiable risk factors for dementia, including body mass index and smoking.

The current study could not determine the biological explanation for the increased dementia risk among older opioid users. “Causal notions are challenging in observational studies and should be viewed with caution,” Dr. Levine noted.

However, a plausible mechanism highlighted in the literature is that opioids promote apoptosis of microglia and neurons that contribute to neurodegenerative diseases, he said.

The study included 14 sensitivity analyses, including those that looked at females, subjects older than 70, smokers, and groups with and without comorbid health conditions. The only sensitivity analysis that didn’t have similar findings to the primary analysis looked at dementia risk restricted to subjects without a vitamin deficiency.

“It’s reassuring that 13 or 14 sensitivity analyses found a significant association between opioid exposure and dementia risk,” said Dr. Levine.

Some prior studies did not show an association between opioid exposure and dementia risk. One possible reason for the discrepancy with the current findings is that the previous research didn’t account for age-specific opioid use effects, or the competing risk of mortality, said Dr. Levine.

Clinicians have a number of potential alternatives to opioids to treat various conditions including acetaminophen, non-steroidal anti-inflammatory drugs, amine reuptake inhibitors (ARIs), membrane stabilizers, muscle relaxants, topical capsaicin, botulinum toxin, cannabinoids, and steroids.

A limitation of the study was that it didn’t adjust for all possible comorbid health conditions, including vascular conditions, or for use of benzodiazepines, and surgical procedures.

In addition, since up to 50% of dementia cases are undetected, it’s possible some in the unexposed opioid group may actually have undiagnosed dementia, thereby reducing the effect sizes in the results.

Reverse causality is also a possibility as the neuropathological process associated with dementia could have started prior to opioid exposure. In addition, the results are limited to prolonged opioid exposure.
 

Interpret with caution

Commenting on the study, David Knopman, MD, a neurologist at Mayo Clinic in Rochester, Minn., whose research involves late-life cognitive disorders, was skeptical.

“On the face of it, the fact that an association was seen only in one narrow age range – 75+ to 80 years – ought to raise serious suspicion about the reliability and validity of the claim that opioid use is a risk factor for dementia, he said.

Although the researchers performed several sensitivity analyses, including accounting for mortality, “pharmacoepidemiological studies are terribly sensitive to residual biases” related to physician and patient choices related to medication use, added Dr. Knopman.

The claim that opioids are a dementia risk “should be viewed with great caution” and should not influence use of opioids where they’re truly indicated, he said.

“It would be a great pity if patients with pain requiring opioids avoid them because of fears about dementia based on the dubious relationship between age and opioid use.”

Dr. Levine and Dr. Knopman report no relevant financial disclosures.

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

NATIONAL HARBOR, MD. – Treating neuromyelitis optica spectrum disorder (NMOSD) with the recently approved monoclonal antibody inebilizumab (Uplizna, Horizon Therapeutics) is effective across patient genotypes – including a common genetic variation linked to reduced response to anti-CD20 therapies, new research shows.

The phase 3 N-MOmentum Study previously showed safety and efficacy for inebilizumab over placebo in more than 200 adults with NMOSD.

A new analysis focused on participants who were carriers of either the F/F allele, which is known to reduce the effectiveness of certain monoclonal antibodies, or the rs396991 V-allele, which has not been associated with a reduced response.

Results showed no significant differences between the two carrier groups in NMOSD activity, including annual rates of new/enlarging T2 lesions, during the trial and up to 6 months after treatment with inebilizumab.

“These data illustrate how mechanistic precision in treatment design can help patients gain benefit from their regimen regardless of the genetic make-up of their immune systems,” coinvestigator Bruce Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco, Weill Institute for Neurosciences, said in a press release.

“The combination of efficacy, safety, and ease of administration with twice-yearly infusions make this product an excellent choice for first-line therapy in NMOSD,” Dr. Cree said.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
 

B-cell depletion

Inebilizumab has also been approved in China, Japan, and South Korea for the treatment of NMOSD, a rare and severe autoantibody-mediated disease of the central nervous system that includes NMO and related syndromes.

The drug’s B-cell depletion capability is credited with reducing inflammation, lesion formation, and astrocyte damage. The latter can cause severe effects in an NMOSD attack, affecting the optic nerve, spinal cord, and brain.

Manifestations can range from loss of vision to paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain or respiratory failure. Attacks can also result in cumulative damage and disability, the researchers noted.

Results from the original double-blind trial of 230 adults with NMOSD showed that treatment with inebilizumab demonstrated efficacy and safety over placebo. However, questions have remained regarding the treatment’s effectiveness, specifically among patients with the FCGR3A (F/F) allele, a genetic variant that encodes the low-affinity Fc gamma receptor IIIa.

This genotype is known to reduce the effectiveness of certain monoclonal antibodies and anti-CD20 therapies, notably rituximab, in disorders such as NMOSD.

With up to 40% of White and Black individuals known to carry the F/F allele, inebilizumab was designed specifically with that risk in mind, with strong binding to the allele.

Although inebilizumab joins two other Food and Drug Administration–approved treatments for NMOSD – eculizumab and satralizumab – neither of those have a mechanism involving the FCGRA3 receptor. Therefore, those drugs are not a concern for individuals with those genotypes.

To evaluate inebilizumab’s effects among patients with the F/F allele, Dr. Cree and colleagues assessed data on a subset of 142 patients from the N-MOmentum trial.

The study included a 28-week randomized controlled period in which adults with NMOSD received either 300 mg of intravenous inebilizumab or placebo on days 1 and 15, followed by an optional open-label period of at least 2 years. During the open-label phase, all patients received 300 mg of IV inebilizumab every 26 weeks.

Of the 142 patients in the genetic analysis, 104 received inebilizumab and 38 received placebo. In addition, 68 group participants were carriers of the F/F allele, while 74 carried the rs396991 V-allele.
 

No significant differences

Prior to the trial, annualized attack rates (AARs) and disability, as assessed by change in the Expanded Disability Status Scale (EDSS) scores, were nominally higher in the V allele group from disease onset to trial enrollment.

During the trial’s first 6 months, AARs and annual rates of new/enlarging T2 lesions were nominally lower in inebilizumab-treated V allele participants compared with the F/F allele participants, although the differences were not statistically significant.

The AAR was 0.1 for the V allele group vs. 0.3 for the F/F allele group (hazard ratio, 0.40; P = .17). The annual rate of new/enlarging T2 lesions was 1.4 vs. 1.7 (risk ratio, 0.91; P = .88), respectively.

However, at the end of the randomized controlled period, there were no significant differences between the two genotype groups. There was also little difference in clinical metrics of NMOSD activity or B-cell depletion between the two genotype groups during the open-label period involving the long-term repeated inebilizumab dosing.

“Though greater B-cell depletion was observed in inebilizumab-treated V allele participants, compared with F/F participants during the first 6 months, no significant difference in NMOSD activity was observed during this time period,” the investigators reported.

“No differences in B-cell depletion or NMOSD disease activity were observed after 6 months of inebilizumab treatment,” they added.

Dr. Cree noted the study showed that, overall, inebiluzumab’s efficacy was not adversely affected by a polymorphism in the Fc gamma receptor. “These types of genetic analyses may help inform future screening mechanisms to tailor treatment strategies that can optimize the response rate for each patient,” he said.

Dr. Cree added the higher degree of disease activity among those carrying the alleles at baseline is notable and deserves further investigation. That finding “suggests that the presence of the F/F allele is to some extent protective of the detrimental effects the auto-antibody directed against aquaporin-4 that underlies NMOSD pathogenesis,” he said.
 

A new era?

Commenting on the study, Marcelo Matiello, MD, assistant professor of neurology at Harvard Medical School and associate director of the Neuromyelitis Optica clinic at Massachusetts General Hospital, both in Boston, said the findings provide valuable insights into risks for key patient subgroups.

“The data is quite important because we know that with other conditions, such as rheumatoid arthritis, people with this particular genotype do have lower response and are more likely to be refractory,” said Dr. Matiello, who was not involved with the research.

He noted that rituximab is the most commonly used medication in the United States for NMOSD. “It’s not FDA approved, but because of extensive experience, and many case series and small prospective studies, most NMO patients are using rituximab,” Dr. Matiello said. However, the drug’s mechanism “can be compromised” by the F/F allele, he added.

The new findings “provide a good understanding that this medication would likely be superior to patients with this genotype,” he said.

“I think it’s a new era,” Dr. Matiello added. “Not only do we have approved medication for this very severe disease, but we can find out who can benefit most. So, I think this is exciting and is a major step in more individualized appropriate use.”

The study was funded by Horizon Therapeutics. Dr. Cree has consulted for Horizon Therapeutics. Dr. Matiello reported no relevant financial relationships.

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

NATIONAL HARBOR, MD. – Treating neuromyelitis optica spectrum disorder (NMOSD) with the recently approved monoclonal antibody inebilizumab (Uplizna, Horizon Therapeutics) is effective across patient genotypes – including a common genetic variation linked to reduced response to anti-CD20 therapies, new research shows.

The phase 3 N-MOmentum Study previously showed safety and efficacy for inebilizumab over placebo in more than 200 adults with NMOSD.

A new analysis focused on participants who were carriers of either the F/F allele, which is known to reduce the effectiveness of certain monoclonal antibodies, or the rs396991 V-allele, which has not been associated with a reduced response.

Results showed no significant differences between the two carrier groups in NMOSD activity, including annual rates of new/enlarging T2 lesions, during the trial and up to 6 months after treatment with inebilizumab.

“These data illustrate how mechanistic precision in treatment design can help patients gain benefit from their regimen regardless of the genetic make-up of their immune systems,” coinvestigator Bruce Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco, Weill Institute for Neurosciences, said in a press release.

“The combination of efficacy, safety, and ease of administration with twice-yearly infusions make this product an excellent choice for first-line therapy in NMOSD,” Dr. Cree said.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
 

B-cell depletion

Inebilizumab has also been approved in China, Japan, and South Korea for the treatment of NMOSD, a rare and severe autoantibody-mediated disease of the central nervous system that includes NMO and related syndromes.

The drug’s B-cell depletion capability is credited with reducing inflammation, lesion formation, and astrocyte damage. The latter can cause severe effects in an NMOSD attack, affecting the optic nerve, spinal cord, and brain.

Manifestations can range from loss of vision to paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain or respiratory failure. Attacks can also result in cumulative damage and disability, the researchers noted.

Results from the original double-blind trial of 230 adults with NMOSD showed that treatment with inebilizumab demonstrated efficacy and safety over placebo. However, questions have remained regarding the treatment’s effectiveness, specifically among patients with the FCGR3A (F/F) allele, a genetic variant that encodes the low-affinity Fc gamma receptor IIIa.

This genotype is known to reduce the effectiveness of certain monoclonal antibodies and anti-CD20 therapies, notably rituximab, in disorders such as NMOSD.

With up to 40% of White and Black individuals known to carry the F/F allele, inebilizumab was designed specifically with that risk in mind, with strong binding to the allele.

Although inebilizumab joins two other Food and Drug Administration–approved treatments for NMOSD – eculizumab and satralizumab – neither of those have a mechanism involving the FCGRA3 receptor. Therefore, those drugs are not a concern for individuals with those genotypes.

To evaluate inebilizumab’s effects among patients with the F/F allele, Dr. Cree and colleagues assessed data on a subset of 142 patients from the N-MOmentum trial.

The study included a 28-week randomized controlled period in which adults with NMOSD received either 300 mg of intravenous inebilizumab or placebo on days 1 and 15, followed by an optional open-label period of at least 2 years. During the open-label phase, all patients received 300 mg of IV inebilizumab every 26 weeks.

Of the 142 patients in the genetic analysis, 104 received inebilizumab and 38 received placebo. In addition, 68 group participants were carriers of the F/F allele, while 74 carried the rs396991 V-allele.
 

No significant differences

Prior to the trial, annualized attack rates (AARs) and disability, as assessed by change in the Expanded Disability Status Scale (EDSS) scores, were nominally higher in the V allele group from disease onset to trial enrollment.

During the trial’s first 6 months, AARs and annual rates of new/enlarging T2 lesions were nominally lower in inebilizumab-treated V allele participants compared with the F/F allele participants, although the differences were not statistically significant.

The AAR was 0.1 for the V allele group vs. 0.3 for the F/F allele group (hazard ratio, 0.40; P = .17). The annual rate of new/enlarging T2 lesions was 1.4 vs. 1.7 (risk ratio, 0.91; P = .88), respectively.

However, at the end of the randomized controlled period, there were no significant differences between the two genotype groups. There was also little difference in clinical metrics of NMOSD activity or B-cell depletion between the two genotype groups during the open-label period involving the long-term repeated inebilizumab dosing.

“Though greater B-cell depletion was observed in inebilizumab-treated V allele participants, compared with F/F participants during the first 6 months, no significant difference in NMOSD activity was observed during this time period,” the investigators reported.

“No differences in B-cell depletion or NMOSD disease activity were observed after 6 months of inebilizumab treatment,” they added.

Dr. Cree noted the study showed that, overall, inebiluzumab’s efficacy was not adversely affected by a polymorphism in the Fc gamma receptor. “These types of genetic analyses may help inform future screening mechanisms to tailor treatment strategies that can optimize the response rate for each patient,” he said.

Dr. Cree added the higher degree of disease activity among those carrying the alleles at baseline is notable and deserves further investigation. That finding “suggests that the presence of the F/F allele is to some extent protective of the detrimental effects the auto-antibody directed against aquaporin-4 that underlies NMOSD pathogenesis,” he said.
 

A new era?

Commenting on the study, Marcelo Matiello, MD, assistant professor of neurology at Harvard Medical School and associate director of the Neuromyelitis Optica clinic at Massachusetts General Hospital, both in Boston, said the findings provide valuable insights into risks for key patient subgroups.

“The data is quite important because we know that with other conditions, such as rheumatoid arthritis, people with this particular genotype do have lower response and are more likely to be refractory,” said Dr. Matiello, who was not involved with the research.

He noted that rituximab is the most commonly used medication in the United States for NMOSD. “It’s not FDA approved, but because of extensive experience, and many case series and small prospective studies, most NMO patients are using rituximab,” Dr. Matiello said. However, the drug’s mechanism “can be compromised” by the F/F allele, he added.

The new findings “provide a good understanding that this medication would likely be superior to patients with this genotype,” he said.

“I think it’s a new era,” Dr. Matiello added. “Not only do we have approved medication for this very severe disease, but we can find out who can benefit most. So, I think this is exciting and is a major step in more individualized appropriate use.”

The study was funded by Horizon Therapeutics. Dr. Cree has consulted for Horizon Therapeutics. Dr. Matiello reported no relevant financial relationships.

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

NATIONAL HARBOR, MD. – Treating neuromyelitis optica spectrum disorder (NMOSD) with the recently approved monoclonal antibody inebilizumab (Uplizna, Horizon Therapeutics) is effective across patient genotypes – including a common genetic variation linked to reduced response to anti-CD20 therapies, new research shows.

The phase 3 N-MOmentum Study previously showed safety and efficacy for inebilizumab over placebo in more than 200 adults with NMOSD.

A new analysis focused on participants who were carriers of either the F/F allele, which is known to reduce the effectiveness of certain monoclonal antibodies, or the rs396991 V-allele, which has not been associated with a reduced response.

Results showed no significant differences between the two carrier groups in NMOSD activity, including annual rates of new/enlarging T2 lesions, during the trial and up to 6 months after treatment with inebilizumab.

“These data illustrate how mechanistic precision in treatment design can help patients gain benefit from their regimen regardless of the genetic make-up of their immune systems,” coinvestigator Bruce Cree, MD, PhD, professor of clinical neurology at the University of California, San Francisco, Weill Institute for Neurosciences, said in a press release.

“The combination of efficacy, safety, and ease of administration with twice-yearly infusions make this product an excellent choice for first-line therapy in NMOSD,” Dr. Cree said.

The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
 

B-cell depletion

Inebilizumab has also been approved in China, Japan, and South Korea for the treatment of NMOSD, a rare and severe autoantibody-mediated disease of the central nervous system that includes NMO and related syndromes.

The drug’s B-cell depletion capability is credited with reducing inflammation, lesion formation, and astrocyte damage. The latter can cause severe effects in an NMOSD attack, affecting the optic nerve, spinal cord, and brain.

Manifestations can range from loss of vision to paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain or respiratory failure. Attacks can also result in cumulative damage and disability, the researchers noted.

Results from the original double-blind trial of 230 adults with NMOSD showed that treatment with inebilizumab demonstrated efficacy and safety over placebo. However, questions have remained regarding the treatment’s effectiveness, specifically among patients with the FCGR3A (F/F) allele, a genetic variant that encodes the low-affinity Fc gamma receptor IIIa.

This genotype is known to reduce the effectiveness of certain monoclonal antibodies and anti-CD20 therapies, notably rituximab, in disorders such as NMOSD.

With up to 40% of White and Black individuals known to carry the F/F allele, inebilizumab was designed specifically with that risk in mind, with strong binding to the allele.

Although inebilizumab joins two other Food and Drug Administration–approved treatments for NMOSD – eculizumab and satralizumab – neither of those have a mechanism involving the FCGRA3 receptor. Therefore, those drugs are not a concern for individuals with those genotypes.

To evaluate inebilizumab’s effects among patients with the F/F allele, Dr. Cree and colleagues assessed data on a subset of 142 patients from the N-MOmentum trial.

The study included a 28-week randomized controlled period in which adults with NMOSD received either 300 mg of intravenous inebilizumab or placebo on days 1 and 15, followed by an optional open-label period of at least 2 years. During the open-label phase, all patients received 300 mg of IV inebilizumab every 26 weeks.

Of the 142 patients in the genetic analysis, 104 received inebilizumab and 38 received placebo. In addition, 68 group participants were carriers of the F/F allele, while 74 carried the rs396991 V-allele.
 

No significant differences

Prior to the trial, annualized attack rates (AARs) and disability, as assessed by change in the Expanded Disability Status Scale (EDSS) scores, were nominally higher in the V allele group from disease onset to trial enrollment.

During the trial’s first 6 months, AARs and annual rates of new/enlarging T2 lesions were nominally lower in inebilizumab-treated V allele participants compared with the F/F allele participants, although the differences were not statistically significant.

The AAR was 0.1 for the V allele group vs. 0.3 for the F/F allele group (hazard ratio, 0.40; P = .17). The annual rate of new/enlarging T2 lesions was 1.4 vs. 1.7 (risk ratio, 0.91; P = .88), respectively.

However, at the end of the randomized controlled period, there were no significant differences between the two genotype groups. There was also little difference in clinical metrics of NMOSD activity or B-cell depletion between the two genotype groups during the open-label period involving the long-term repeated inebilizumab dosing.

“Though greater B-cell depletion was observed in inebilizumab-treated V allele participants, compared with F/F participants during the first 6 months, no significant difference in NMOSD activity was observed during this time period,” the investigators reported.

“No differences in B-cell depletion or NMOSD disease activity were observed after 6 months of inebilizumab treatment,” they added.

Dr. Cree noted the study showed that, overall, inebiluzumab’s efficacy was not adversely affected by a polymorphism in the Fc gamma receptor. “These types of genetic analyses may help inform future screening mechanisms to tailor treatment strategies that can optimize the response rate for each patient,” he said.

Dr. Cree added the higher degree of disease activity among those carrying the alleles at baseline is notable and deserves further investigation. That finding “suggests that the presence of the F/F allele is to some extent protective of the detrimental effects the auto-antibody directed against aquaporin-4 that underlies NMOSD pathogenesis,” he said.
 

A new era?

Commenting on the study, Marcelo Matiello, MD, assistant professor of neurology at Harvard Medical School and associate director of the Neuromyelitis Optica clinic at Massachusetts General Hospital, both in Boston, said the findings provide valuable insights into risks for key patient subgroups.

“The data is quite important because we know that with other conditions, such as rheumatoid arthritis, people with this particular genotype do have lower response and are more likely to be refractory,” said Dr. Matiello, who was not involved with the research.

He noted that rituximab is the most commonly used medication in the United States for NMOSD. “It’s not FDA approved, but because of extensive experience, and many case series and small prospective studies, most NMO patients are using rituximab,” Dr. Matiello said. However, the drug’s mechanism “can be compromised” by the F/F allele, he added.

The new findings “provide a good understanding that this medication would likely be superior to patients with this genotype,” he said.

“I think it’s a new era,” Dr. Matiello added. “Not only do we have approved medication for this very severe disease, but we can find out who can benefit most. So, I think this is exciting and is a major step in more individualized appropriate use.”

The study was funded by Horizon Therapeutics. Dr. Cree has consulted for Horizon Therapeutics. Dr. Matiello reported no relevant financial relationships.

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

MILAN, Italy – The antisense oligonucleotide vupanorsen substantially reduces very-low-density-lipoprotein (VLDL) and remnant cholesterol levels in patients with raised lipids despite statin therapy, suggests a subanalysis of TRANSLATE-TIMI 70 that appears to offer more hope than the primary study findings.

Vupanorsen targets hepatic angiopoietin-like protein 3 (ANGPTL3), which inhibits enzymes involved in triglyceride and cholesterol metabolism.

Earlier this year, headline data from TRANSLATE-TIMI 70 suggested that the drug reduced triglycerides and non–high-density-lipoprotein cholesterol to a degree that was significant but not clinically meaningful for cardiovascular risk reduction.

Moreover, as reported by this news organization, there were safety concerns over increases in liver enzymes among patients taking the drug, as well as dose-related increases in hepatic fat.

As a result, Pfizer announced that it would discontinue its clinical development program for vupanorsen and return the development rights to Ionis, following the signing of a worldwide exclusive agreement in November 2019.

Now, Nicholas A. Marston, MD, MPH, cardiovascular medicine, Brigham and Women’s Hospital, Boston, has presented a post-hoc analysis of the phase 2b study, showing that the drug reduces VLDL and remnant cholesterol levels by up to 60%.

These were closely tied to reductions in ANGPTL3 levels, although substantial reductions in cholesterol levels were achieved even at less than maximal reductions in ANGPTL3, where the impact on safety outcomes was reduced.

Dr. Marston said that lower doses of vupanorsen, where the safety effects would be less, or other drugs that inhibit ANGPTL3, “may have an important role in patients with residual dyslipidemia despite current therapy.”

The results were presented at the 90th European Atherosclerosis Society Congress on May 23.

Dr. Marston told this news organization that some of the reductions they saw with the lower doses of vupanorsen were “just as good as any other therapy, and the safety profile was … much better than at the highest dose.”

They wanted to pursue the subgroup analysis, despite Pfizer’s announcement, partly to “learn something in terms of the potential efficacy of the ANGPTL3 pathway in general.”

Dr. Marston said that Ionis is now focused on ANGPTL3, and the current results suggest that it “works very well,” so if other drugs are able to achieve the same efficacy as vupanorsen “but without the effects,” then it may “get elbowed out.”

Børge G. Nordestgaard, MD, PhD, of Herlev and Gentofte Hospital, Copenhagen, who was not involved in the study, called the findings “very encouraging.”

He told this news organization that being able to reduce LDL cholesterol as well as VLDL and remnant cholesterol is “exactly what I would be dreaming about” with a drug like vupanorsen.

Dr. Nordestgaard nevertheless underlined that “one would have to look carefully” at the safety of the drug.

“If it was my money, I would certainly try to look into if this was some sort of transient thing. Even when they started talking about statins, there was also this transient increase in alanine transaminase that seems to go away after a while,” he said.

“But of course, if this was persistent and triglycerides in the liver kept accumulating, then it’s a problem,” Dr. Nordestgaard added, “and then you would need to have some sort of thinking about whether you could couple it with something that got rid of the liver fat.”

He also agreed with Dr. Marston that, even if vupanorsen does not clear all hurdles before making it to market, the approach is promising.

“The target,” Dr. Nordestgaard said, seems “fantastic, from my point of view anyway.”

Dr. Marston explained that VLDL cholesterol, remnant cholesterol, and triglycerides are “surrogates for triglyceride-rich” lipoproteins, and that they are “increasingly recognized” as cardiovascular risk factors.

He highlighted that currently available therapies achieve reductions of these compounds of between 30% and 50%.

TRANSLATE-TIMI 70 included adults on stable statin therapy who had a triglyceride level of 150 mg/dL to 500 mg/dL and a non-HDL cholesterol level of 100 mg/dL or higher.

The participants were randomly assigned to one of six 2- or 4-week dosing schedules of vupanorsen or placebo and followed up over 24 weeks for a series of primary and additional endpoints, as well as safety outcomes.

The team recruited 286 individuals, who had a median age of 64 years; 44% were female. The majority (87%) were white.

The mean body mass index was 32 kg/m², 50% had diabetes, 13% had experienced a prior myocardial infarction, and 51% were receiving high-intensity statins.

As previously reported, vupanorsen was associated with a reduction in non-HDL cholesterol vs. placebo of 22%-28%, alongside a 6%-15% reduction in apolipoprotein B levels and an 8%-16% reduction in LDL cholesterol.

In contrast, Dr. Marston showed that the various dosing schedules of the drug were associated with reductions in levels of VLDL cholesterol of 52%-66% vs. placebo at 24 weeks.

Over the same period, remnant cholesterol levels were lowered by 42%-59% vs. placebo, and triglycerides were reduced by 44%-57% in patients given vupanorsen.

There were also reductions in ANGPTL3 levels of 70%-95%.

Subgroup analysis indicated that the effect of vupanorsen was seen regardless of age, sex, body mass index, presence of diabetes, baseline triglycerides, and intensity of statin therapy.

Dr. Marston highlighted that the reductions in triglycerides, VLDL cholesterol, and remnant cholesterol levels were directly related to those for ANGPTL3 levels, but that the reductions remained meaningful even at less than maximal reductions in ANGPTL.

For example, even when ANGPTL3 levels were reduced by 70%, there were 50% reductions in triglyceride levels, 70% reductions in VLDL cholesterol levels, and a 50% drop in remnant cholesterol levels.

This, he noted, is important given that safety signals such as increases in alanine transaminase and hepatic fat occurred in a dose-dependent manner with ANGPTL3 reductions and were “most pronounced” only at the highest level of ANGPTL3 reduction.

The TRANSLATE-TIMI 70 study was sponsored by Pfizer. Dr. Marston disclosed relationships with Pfizer, Amgen, Ionis, Novartis, and AstraZeneca. Dr. Nordestgaard disclosed relationships with AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics.

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

MILAN, Italy – The antisense oligonucleotide vupanorsen substantially reduces very-low-density-lipoprotein (VLDL) and remnant cholesterol levels in patients with raised lipids despite statin therapy, suggests a subanalysis of TRANSLATE-TIMI 70 that appears to offer more hope than the primary study findings.

Vupanorsen targets hepatic angiopoietin-like protein 3 (ANGPTL3), which inhibits enzymes involved in triglyceride and cholesterol metabolism.

Earlier this year, headline data from TRANSLATE-TIMI 70 suggested that the drug reduced triglycerides and non–high-density-lipoprotein cholesterol to a degree that was significant but not clinically meaningful for cardiovascular risk reduction.

Moreover, as reported by this news organization, there were safety concerns over increases in liver enzymes among patients taking the drug, as well as dose-related increases in hepatic fat.

As a result, Pfizer announced that it would discontinue its clinical development program for vupanorsen and return the development rights to Ionis, following the signing of a worldwide exclusive agreement in November 2019.

Now, Nicholas A. Marston, MD, MPH, cardiovascular medicine, Brigham and Women’s Hospital, Boston, has presented a post-hoc analysis of the phase 2b study, showing that the drug reduces VLDL and remnant cholesterol levels by up to 60%.

These were closely tied to reductions in ANGPTL3 levels, although substantial reductions in cholesterol levels were achieved even at less than maximal reductions in ANGPTL3, where the impact on safety outcomes was reduced.

Dr. Marston said that lower doses of vupanorsen, where the safety effects would be less, or other drugs that inhibit ANGPTL3, “may have an important role in patients with residual dyslipidemia despite current therapy.”

The results were presented at the 90th European Atherosclerosis Society Congress on May 23.

Dr. Marston told this news organization that some of the reductions they saw with the lower doses of vupanorsen were “just as good as any other therapy, and the safety profile was … much better than at the highest dose.”

They wanted to pursue the subgroup analysis, despite Pfizer’s announcement, partly to “learn something in terms of the potential efficacy of the ANGPTL3 pathway in general.”

Dr. Marston said that Ionis is now focused on ANGPTL3, and the current results suggest that it “works very well,” so if other drugs are able to achieve the same efficacy as vupanorsen “but without the effects,” then it may “get elbowed out.”

Børge G. Nordestgaard, MD, PhD, of Herlev and Gentofte Hospital, Copenhagen, who was not involved in the study, called the findings “very encouraging.”

He told this news organization that being able to reduce LDL cholesterol as well as VLDL and remnant cholesterol is “exactly what I would be dreaming about” with a drug like vupanorsen.

Dr. Nordestgaard nevertheless underlined that “one would have to look carefully” at the safety of the drug.

“If it was my money, I would certainly try to look into if this was some sort of transient thing. Even when they started talking about statins, there was also this transient increase in alanine transaminase that seems to go away after a while,” he said.

“But of course, if this was persistent and triglycerides in the liver kept accumulating, then it’s a problem,” Dr. Nordestgaard added, “and then you would need to have some sort of thinking about whether you could couple it with something that got rid of the liver fat.”

He also agreed with Dr. Marston that, even if vupanorsen does not clear all hurdles before making it to market, the approach is promising.

“The target,” Dr. Nordestgaard said, seems “fantastic, from my point of view anyway.”

Dr. Marston explained that VLDL cholesterol, remnant cholesterol, and triglycerides are “surrogates for triglyceride-rich” lipoproteins, and that they are “increasingly recognized” as cardiovascular risk factors.

He highlighted that currently available therapies achieve reductions of these compounds of between 30% and 50%.

TRANSLATE-TIMI 70 included adults on stable statin therapy who had a triglyceride level of 150 mg/dL to 500 mg/dL and a non-HDL cholesterol level of 100 mg/dL or higher.

The participants were randomly assigned to one of six 2- or 4-week dosing schedules of vupanorsen or placebo and followed up over 24 weeks for a series of primary and additional endpoints, as well as safety outcomes.

The team recruited 286 individuals, who had a median age of 64 years; 44% were female. The majority (87%) were white.

The mean body mass index was 32 kg/m², 50% had diabetes, 13% had experienced a prior myocardial infarction, and 51% were receiving high-intensity statins.

As previously reported, vupanorsen was associated with a reduction in non-HDL cholesterol vs. placebo of 22%-28%, alongside a 6%-15% reduction in apolipoprotein B levels and an 8%-16% reduction in LDL cholesterol.

In contrast, Dr. Marston showed that the various dosing schedules of the drug were associated with reductions in levels of VLDL cholesterol of 52%-66% vs. placebo at 24 weeks.

Over the same period, remnant cholesterol levels were lowered by 42%-59% vs. placebo, and triglycerides were reduced by 44%-57% in patients given vupanorsen.

There were also reductions in ANGPTL3 levels of 70%-95%.

Subgroup analysis indicated that the effect of vupanorsen was seen regardless of age, sex, body mass index, presence of diabetes, baseline triglycerides, and intensity of statin therapy.

Dr. Marston highlighted that the reductions in triglycerides, VLDL cholesterol, and remnant cholesterol levels were directly related to those for ANGPTL3 levels, but that the reductions remained meaningful even at less than maximal reductions in ANGPTL.

For example, even when ANGPTL3 levels were reduced by 70%, there were 50% reductions in triglyceride levels, 70% reductions in VLDL cholesterol levels, and a 50% drop in remnant cholesterol levels.

This, he noted, is important given that safety signals such as increases in alanine transaminase and hepatic fat occurred in a dose-dependent manner with ANGPTL3 reductions and were “most pronounced” only at the highest level of ANGPTL3 reduction.

The TRANSLATE-TIMI 70 study was sponsored by Pfizer. Dr. Marston disclosed relationships with Pfizer, Amgen, Ionis, Novartis, and AstraZeneca. Dr. Nordestgaard disclosed relationships with AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics.

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

MILAN, Italy – The antisense oligonucleotide vupanorsen substantially reduces very-low-density-lipoprotein (VLDL) and remnant cholesterol levels in patients with raised lipids despite statin therapy, suggests a subanalysis of TRANSLATE-TIMI 70 that appears to offer more hope than the primary study findings.

Vupanorsen targets hepatic angiopoietin-like protein 3 (ANGPTL3), which inhibits enzymes involved in triglyceride and cholesterol metabolism.

Earlier this year, headline data from TRANSLATE-TIMI 70 suggested that the drug reduced triglycerides and non–high-density-lipoprotein cholesterol to a degree that was significant but not clinically meaningful for cardiovascular risk reduction.

Moreover, as reported by this news organization, there were safety concerns over increases in liver enzymes among patients taking the drug, as well as dose-related increases in hepatic fat.

As a result, Pfizer announced that it would discontinue its clinical development program for vupanorsen and return the development rights to Ionis, following the signing of a worldwide exclusive agreement in November 2019.

Now, Nicholas A. Marston, MD, MPH, cardiovascular medicine, Brigham and Women’s Hospital, Boston, has presented a post-hoc analysis of the phase 2b study, showing that the drug reduces VLDL and remnant cholesterol levels by up to 60%.

These were closely tied to reductions in ANGPTL3 levels, although substantial reductions in cholesterol levels were achieved even at less than maximal reductions in ANGPTL3, where the impact on safety outcomes was reduced.

Dr. Marston said that lower doses of vupanorsen, where the safety effects would be less, or other drugs that inhibit ANGPTL3, “may have an important role in patients with residual dyslipidemia despite current therapy.”

The results were presented at the 90th European Atherosclerosis Society Congress on May 23.

Dr. Marston told this news organization that some of the reductions they saw with the lower doses of vupanorsen were “just as good as any other therapy, and the safety profile was … much better than at the highest dose.”

They wanted to pursue the subgroup analysis, despite Pfizer’s announcement, partly to “learn something in terms of the potential efficacy of the ANGPTL3 pathway in general.”

Dr. Marston said that Ionis is now focused on ANGPTL3, and the current results suggest that it “works very well,” so if other drugs are able to achieve the same efficacy as vupanorsen “but without the effects,” then it may “get elbowed out.”

Børge G. Nordestgaard, MD, PhD, of Herlev and Gentofte Hospital, Copenhagen, who was not involved in the study, called the findings “very encouraging.”

He told this news organization that being able to reduce LDL cholesterol as well as VLDL and remnant cholesterol is “exactly what I would be dreaming about” with a drug like vupanorsen.

Dr. Nordestgaard nevertheless underlined that “one would have to look carefully” at the safety of the drug.

“If it was my money, I would certainly try to look into if this was some sort of transient thing. Even when they started talking about statins, there was also this transient increase in alanine transaminase that seems to go away after a while,” he said.

“But of course, if this was persistent and triglycerides in the liver kept accumulating, then it’s a problem,” Dr. Nordestgaard added, “and then you would need to have some sort of thinking about whether you could couple it with something that got rid of the liver fat.”

He also agreed with Dr. Marston that, even if vupanorsen does not clear all hurdles before making it to market, the approach is promising.

“The target,” Dr. Nordestgaard said, seems “fantastic, from my point of view anyway.”

Dr. Marston explained that VLDL cholesterol, remnant cholesterol, and triglycerides are “surrogates for triglyceride-rich” lipoproteins, and that they are “increasingly recognized” as cardiovascular risk factors.

He highlighted that currently available therapies achieve reductions of these compounds of between 30% and 50%.

TRANSLATE-TIMI 70 included adults on stable statin therapy who had a triglyceride level of 150 mg/dL to 500 mg/dL and a non-HDL cholesterol level of 100 mg/dL or higher.

The participants were randomly assigned to one of six 2- or 4-week dosing schedules of vupanorsen or placebo and followed up over 24 weeks for a series of primary and additional endpoints, as well as safety outcomes.

The team recruited 286 individuals, who had a median age of 64 years; 44% were female. The majority (87%) were white.

The mean body mass index was 32 kg/m², 50% had diabetes, 13% had experienced a prior myocardial infarction, and 51% were receiving high-intensity statins.

As previously reported, vupanorsen was associated with a reduction in non-HDL cholesterol vs. placebo of 22%-28%, alongside a 6%-15% reduction in apolipoprotein B levels and an 8%-16% reduction in LDL cholesterol.

In contrast, Dr. Marston showed that the various dosing schedules of the drug were associated with reductions in levels of VLDL cholesterol of 52%-66% vs. placebo at 24 weeks.

Over the same period, remnant cholesterol levels were lowered by 42%-59% vs. placebo, and triglycerides were reduced by 44%-57% in patients given vupanorsen.

There were also reductions in ANGPTL3 levels of 70%-95%.

Subgroup analysis indicated that the effect of vupanorsen was seen regardless of age, sex, body mass index, presence of diabetes, baseline triglycerides, and intensity of statin therapy.

Dr. Marston highlighted that the reductions in triglycerides, VLDL cholesterol, and remnant cholesterol levels were directly related to those for ANGPTL3 levels, but that the reductions remained meaningful even at less than maximal reductions in ANGPTL.

For example, even when ANGPTL3 levels were reduced by 70%, there were 50% reductions in triglyceride levels, 70% reductions in VLDL cholesterol levels, and a 50% drop in remnant cholesterol levels.

This, he noted, is important given that safety signals such as increases in alanine transaminase and hepatic fat occurred in a dose-dependent manner with ANGPTL3 reductions and were “most pronounced” only at the highest level of ANGPTL3 reduction.

The TRANSLATE-TIMI 70 study was sponsored by Pfizer. Dr. Marston disclosed relationships with Pfizer, Amgen, Ionis, Novartis, and AstraZeneca. Dr. Nordestgaard disclosed relationships with AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

NEW ORLEANS – In an unexpected finding, researchers discovered that Asian American adolescents had the highest rate of suicidal ideation, per a 2019 national survey of high-school students. According to a weighted analysis, 24% of Asian Americans reported thinking about or planning suicide vs. 22% of Whites and Blacks and 20% of Hispanics (P < .01).

“We were shocked,” said study lead author Esha Hansoti, MD, who conducted the research at UT Southwestern Medical Center, Dallas, and is now a psychiatry resident at Zucker Hillside Hospital Northwell/Hofstra in Glen Oaks, NY. The findings were released at the annual meeting of the American Psychiatric Association.

Dr. Hansoti and colleagues launched the analysis in light of sparse research into Asian American mental health, she said. Even within this population, she said, mental illness “tends to be overlooked” and discussion of the topic may be considered taboo.

For the new study, researchers analyzed the 2019 Youth Risk Behavior Survey, conducted biennially by the Centers for Disease Control and Prevention, which had more than 13,000 participants in grades 9-12.

A weighted bivariate analysis of 618 Asian American adolescents – adjusted for age, sex, and depressive symptoms – found no statistically significant impact on suicidal ideation by gender, age, substance use, sexual/physical dating violence, or fluency in English.

However, several groups had a statistically significant higher risk, including victims of forced sexual intercourse and those who were threatened or bullied at school.

Those who didn’t get mostly A grades were also at high risk: Adolescents with mostly Ds and Fs were more likely to have acknowledged suicidal ideation than those with mostly As (adjusted odds ratio [AOR] = 3.2).

Gays and lesbians (AOR = 7.9 vs. heterosexuals), and bisexuals (AOR = 5.2 vs. heterosexuals) also showed sharply higher rates of suicidal ideation.

It’s not clear why Asian American adolescents may be at higher risk of suicidal ideation. The survey was completed prior to the COVID-19 pandemic, which spawned bigotry against people of Asian descent and an ongoing outbreak of high-profile violence against Asian Americans across the country.

Dr. Hansoti noted that Asian Americans face the pressures to live up to the standards of being a “model minority.” In addition, “very few Asian American adolescents are taken to a therapist, and few mental health providers are Asian Americans.”

She urged fellow psychiatrists “to remember that our perceptions of Asian Americans might hinder some of the diagnoses we could be making. Be thoughtful about how their ethnicity and race affects their presentation and their own perception of their illness.”

She added that Asian Americans may experience mental illness and anxiety “more somatically and physically than emotionally.”

In an interview, Anne Saw, PhD, associate professor of clinical-community psychology at DePaul University, Chicago, said the findings are “helpful for corroborating other studies identifying risk factors of suicidal ideation among Asian American adolescents. Since this research utilizes the Youth Risk Behavior Survey, these findings can be compared with risk factors of suicidal ideation among adolescents from other racial/ethnic backgrounds to pinpoint general as well as specific risk factors, thus informing how we can tailor interventions for specific groups.”

According to Dr. Saw, while it’s clear that suicide is a leading cause of death among Asian American adolescents, it’s still unknown which specific subgroups other than girls and LGBTIA+ individuals are especially vulnerable and which culturally tailored interventions are most effective for decreasing suicide risk.

“Psychiatrists should understand that risk and protective factors for suicidal behavior in Asian American adolescents are multifaceted and require careful attention and intervention across different environments,” she said.

No funding and no disclosures were reported.

NEW ORLEANS – In an unexpected finding, researchers discovered that Asian American adolescents had the highest rate of suicidal ideation, per a 2019 national survey of high-school students. According to a weighted analysis, 24% of Asian Americans reported thinking about or planning suicide vs. 22% of Whites and Blacks and 20% of Hispanics (P < .01).

“We were shocked,” said study lead author Esha Hansoti, MD, who conducted the research at UT Southwestern Medical Center, Dallas, and is now a psychiatry resident at Zucker Hillside Hospital Northwell/Hofstra in Glen Oaks, NY. The findings were released at the annual meeting of the American Psychiatric Association.

Dr. Hansoti and colleagues launched the analysis in light of sparse research into Asian American mental health, she said. Even within this population, she said, mental illness “tends to be overlooked” and discussion of the topic may be considered taboo.

For the new study, researchers analyzed the 2019 Youth Risk Behavior Survey, conducted biennially by the Centers for Disease Control and Prevention, which had more than 13,000 participants in grades 9-12.

A weighted bivariate analysis of 618 Asian American adolescents – adjusted for age, sex, and depressive symptoms – found no statistically significant impact on suicidal ideation by gender, age, substance use, sexual/physical dating violence, or fluency in English.

However, several groups had a statistically significant higher risk, including victims of forced sexual intercourse and those who were threatened or bullied at school.

Those who didn’t get mostly A grades were also at high risk: Adolescents with mostly Ds and Fs were more likely to have acknowledged suicidal ideation than those with mostly As (adjusted odds ratio [AOR] = 3.2).

Gays and lesbians (AOR = 7.9 vs. heterosexuals), and bisexuals (AOR = 5.2 vs. heterosexuals) also showed sharply higher rates of suicidal ideation.

It’s not clear why Asian American adolescents may be at higher risk of suicidal ideation. The survey was completed prior to the COVID-19 pandemic, which spawned bigotry against people of Asian descent and an ongoing outbreak of high-profile violence against Asian Americans across the country.

Dr. Hansoti noted that Asian Americans face the pressures to live up to the standards of being a “model minority.” In addition, “very few Asian American adolescents are taken to a therapist, and few mental health providers are Asian Americans.”

She urged fellow psychiatrists “to remember that our perceptions of Asian Americans might hinder some of the diagnoses we could be making. Be thoughtful about how their ethnicity and race affects their presentation and their own perception of their illness.”

She added that Asian Americans may experience mental illness and anxiety “more somatically and physically than emotionally.”

In an interview, Anne Saw, PhD, associate professor of clinical-community psychology at DePaul University, Chicago, said the findings are “helpful for corroborating other studies identifying risk factors of suicidal ideation among Asian American adolescents. Since this research utilizes the Youth Risk Behavior Survey, these findings can be compared with risk factors of suicidal ideation among adolescents from other racial/ethnic backgrounds to pinpoint general as well as specific risk factors, thus informing how we can tailor interventions for specific groups.”

According to Dr. Saw, while it’s clear that suicide is a leading cause of death among Asian American adolescents, it’s still unknown which specific subgroups other than girls and LGBTIA+ individuals are especially vulnerable and which culturally tailored interventions are most effective for decreasing suicide risk.

“Psychiatrists should understand that risk and protective factors for suicidal behavior in Asian American adolescents are multifaceted and require careful attention and intervention across different environments,” she said.

No funding and no disclosures were reported.

NEW ORLEANS – In an unexpected finding, researchers discovered that Asian American adolescents had the highest rate of suicidal ideation, per a 2019 national survey of high-school students. According to a weighted analysis, 24% of Asian Americans reported thinking about or planning suicide vs. 22% of Whites and Blacks and 20% of Hispanics (P < .01).

“We were shocked,” said study lead author Esha Hansoti, MD, who conducted the research at UT Southwestern Medical Center, Dallas, and is now a psychiatry resident at Zucker Hillside Hospital Northwell/Hofstra in Glen Oaks, NY. The findings were released at the annual meeting of the American Psychiatric Association.

Dr. Hansoti and colleagues launched the analysis in light of sparse research into Asian American mental health, she said. Even within this population, she said, mental illness “tends to be overlooked” and discussion of the topic may be considered taboo.

For the new study, researchers analyzed the 2019 Youth Risk Behavior Survey, conducted biennially by the Centers for Disease Control and Prevention, which had more than 13,000 participants in grades 9-12.

A weighted bivariate analysis of 618 Asian American adolescents – adjusted for age, sex, and depressive symptoms – found no statistically significant impact on suicidal ideation by gender, age, substance use, sexual/physical dating violence, or fluency in English.

However, several groups had a statistically significant higher risk, including victims of forced sexual intercourse and those who were threatened or bullied at school.

Those who didn’t get mostly A grades were also at high risk: Adolescents with mostly Ds and Fs were more likely to have acknowledged suicidal ideation than those with mostly As (adjusted odds ratio [AOR] = 3.2).

Gays and lesbians (AOR = 7.9 vs. heterosexuals), and bisexuals (AOR = 5.2 vs. heterosexuals) also showed sharply higher rates of suicidal ideation.

It’s not clear why Asian American adolescents may be at higher risk of suicidal ideation. The survey was completed prior to the COVID-19 pandemic, which spawned bigotry against people of Asian descent and an ongoing outbreak of high-profile violence against Asian Americans across the country.

Dr. Hansoti noted that Asian Americans face the pressures to live up to the standards of being a “model minority.” In addition, “very few Asian American adolescents are taken to a therapist, and few mental health providers are Asian Americans.”

She urged fellow psychiatrists “to remember that our perceptions of Asian Americans might hinder some of the diagnoses we could be making. Be thoughtful about how their ethnicity and race affects their presentation and their own perception of their illness.”

She added that Asian Americans may experience mental illness and anxiety “more somatically and physically than emotionally.”

In an interview, Anne Saw, PhD, associate professor of clinical-community psychology at DePaul University, Chicago, said the findings are “helpful for corroborating other studies identifying risk factors of suicidal ideation among Asian American adolescents. Since this research utilizes the Youth Risk Behavior Survey, these findings can be compared with risk factors of suicidal ideation among adolescents from other racial/ethnic backgrounds to pinpoint general as well as specific risk factors, thus informing how we can tailor interventions for specific groups.”

According to Dr. Saw, while it’s clear that suicide is a leading cause of death among Asian American adolescents, it’s still unknown which specific subgroups other than girls and LGBTIA+ individuals are especially vulnerable and which culturally tailored interventions are most effective for decreasing suicide risk.

“Psychiatrists should understand that risk and protective factors for suicidal behavior in Asian American adolescents are multifaceted and require careful attention and intervention across different environments,” she said.

No funding and no disclosures were reported.

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.