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Why Residents Are Joining Unions in Droves

Article Type
Changed
Tue, 10/08/2024 - 11:04

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

 

 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

 

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

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Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

 

 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

 

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

 

 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

 

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

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Crisugabalin Alleviates Postherpetic Neuralgia Symptoms in Phase 3 Study

Article Type
Changed
Tue, 10/08/2024 - 10:34

 

TOPLINE:

Crisugabalin — an oral calcium channel alpha 2 delta-1 subunit ligand — was safe and well-tolerated at doses of 40 mg/d and 80 mg/d and significantly reduced pain scores in patients with postherpetic neuralgia (PHN) over 12 weeks in a phase 3 study.

METHODOLOGY:

  • Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
  • Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
  • The primary efficacy endpoint was the change in ADPS from baseline at week 12.
  • Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.

TAKEAWAY:

  • At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
  • A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
  • Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
  • Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.

IN PRACTICE:

“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”

SOURCE:

The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.

LIMITATIONS:

The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.

DISCLOSURES:

The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.

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

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TOPLINE:

Crisugabalin — an oral calcium channel alpha 2 delta-1 subunit ligand — was safe and well-tolerated at doses of 40 mg/d and 80 mg/d and significantly reduced pain scores in patients with postherpetic neuralgia (PHN) over 12 weeks in a phase 3 study.

METHODOLOGY:

  • Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
  • Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
  • The primary efficacy endpoint was the change in ADPS from baseline at week 12.
  • Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.

TAKEAWAY:

  • At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
  • A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
  • Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
  • Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.

IN PRACTICE:

“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”

SOURCE:

The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.

LIMITATIONS:

The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.

DISCLOSURES:

The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.

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

 

TOPLINE:

Crisugabalin — an oral calcium channel alpha 2 delta-1 subunit ligand — was safe and well-tolerated at doses of 40 mg/d and 80 mg/d and significantly reduced pain scores in patients with postherpetic neuralgia (PHN) over 12 weeks in a phase 3 study.

METHODOLOGY:

  • Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
  • Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
  • The primary efficacy endpoint was the change in ADPS from baseline at week 12.
  • Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.

TAKEAWAY:

  • At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
  • A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
  • Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
  • Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.

IN PRACTICE:

“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”

SOURCE:

The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.

LIMITATIONS:

The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.

DISCLOSURES:

The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.

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

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Statins for MS (Not)

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Mon, 10/07/2024 - 11:15

Hidden behind all of the new drugs and breakthroughs reported at the 2024 ECTRIMS meetings was one paper that caught my attention.

It was that, after several years of study, simvastatin had no benefit for multiple sclerosis.

Statins for MS (and for Alzheimer’s disease) have been bandied about for some time, with arguments based on theoretical ideas, and small studies, that they’d have a beneficial effect on the disease – maybe from anti-inflammatory and other properties. In addition, they offered the benefit of being widely available and comparatively inexpensive.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block

Because of those studies, 15-20 years ago I used them off label for MS in a handful of patients – sometimes as an adjunct to their current treatment (limited at that point to interferons and Copaxone), or in patients who couldn’t afford the FDA-approved drugs. Although not without their drawbacks, the statins are relatively well understood and tolerated.

At some point, for reasons I’ve long forgotten, they all came off of them (at least for MS purposes). Maybe for side effects, or lack of benefit, or because new medications, with much clearer efficacies, were rolling out.

Now it seems pretty clear that statins don’t work for MS.

So was it a bad idea to try? No. Without asking questions we don’t find answers. If they’d worked out it would have been great, another tool on the neurology workbench to reach for in the right situation. It might also have led us to new avenues in MS treatment.

But it didn’t, and that’s fine. Although they don’t get the attention, we learn as much (sometimes more) from negative studies as we do from positive ones. If we put people on every drug that initially showed promise for their conditions, my patients would have a pretty huge medication list. For Alzheimer’s disease alone I remember studies that once suggested ibuprofen, statins, estrogen, nicotine, and several vitamins might be effective (“might” being the key word). Today we’re looking at the PDE5 inhibitors and semaglutide. The jury is still out on them, but whichever way it goes we’ll still learn something.

The statins are good drugs. Their benefits in cardiac and cerebrovascular disease can’t be disputed (I’m sure someone would, but that’s not the point of this piece). But, like all drugs, they don’t work for everything.

Just like other sciences, everything we do now in medicine is based on both the successes and failures of what came before. We learn from both and keep moving forward.
 

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

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Hidden behind all of the new drugs and breakthroughs reported at the 2024 ECTRIMS meetings was one paper that caught my attention.

It was that, after several years of study, simvastatin had no benefit for multiple sclerosis.

Statins for MS (and for Alzheimer’s disease) have been bandied about for some time, with arguments based on theoretical ideas, and small studies, that they’d have a beneficial effect on the disease – maybe from anti-inflammatory and other properties. In addition, they offered the benefit of being widely available and comparatively inexpensive.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block

Because of those studies, 15-20 years ago I used them off label for MS in a handful of patients – sometimes as an adjunct to their current treatment (limited at that point to interferons and Copaxone), or in patients who couldn’t afford the FDA-approved drugs. Although not without their drawbacks, the statins are relatively well understood and tolerated.

At some point, for reasons I’ve long forgotten, they all came off of them (at least for MS purposes). Maybe for side effects, or lack of benefit, or because new medications, with much clearer efficacies, were rolling out.

Now it seems pretty clear that statins don’t work for MS.

So was it a bad idea to try? No. Without asking questions we don’t find answers. If they’d worked out it would have been great, another tool on the neurology workbench to reach for in the right situation. It might also have led us to new avenues in MS treatment.

But it didn’t, and that’s fine. Although they don’t get the attention, we learn as much (sometimes more) from negative studies as we do from positive ones. If we put people on every drug that initially showed promise for their conditions, my patients would have a pretty huge medication list. For Alzheimer’s disease alone I remember studies that once suggested ibuprofen, statins, estrogen, nicotine, and several vitamins might be effective (“might” being the key word). Today we’re looking at the PDE5 inhibitors and semaglutide. The jury is still out on them, but whichever way it goes we’ll still learn something.

The statins are good drugs. Their benefits in cardiac and cerebrovascular disease can’t be disputed (I’m sure someone would, but that’s not the point of this piece). But, like all drugs, they don’t work for everything.

Just like other sciences, everything we do now in medicine is based on both the successes and failures of what came before. We learn from both and keep moving forward.
 

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

Hidden behind all of the new drugs and breakthroughs reported at the 2024 ECTRIMS meetings was one paper that caught my attention.

It was that, after several years of study, simvastatin had no benefit for multiple sclerosis.

Statins for MS (and for Alzheimer’s disease) have been bandied about for some time, with arguments based on theoretical ideas, and small studies, that they’d have a beneficial effect on the disease – maybe from anti-inflammatory and other properties. In addition, they offered the benefit of being widely available and comparatively inexpensive.

Dr. Allan M. Block, a neurologist in Scottsdale, Arizona.
Dr. Allan M. Block

Because of those studies, 15-20 years ago I used them off label for MS in a handful of patients – sometimes as an adjunct to their current treatment (limited at that point to interferons and Copaxone), or in patients who couldn’t afford the FDA-approved drugs. Although not without their drawbacks, the statins are relatively well understood and tolerated.

At some point, for reasons I’ve long forgotten, they all came off of them (at least for MS purposes). Maybe for side effects, or lack of benefit, or because new medications, with much clearer efficacies, were rolling out.

Now it seems pretty clear that statins don’t work for MS.

So was it a bad idea to try? No. Without asking questions we don’t find answers. If they’d worked out it would have been great, another tool on the neurology workbench to reach for in the right situation. It might also have led us to new avenues in MS treatment.

But it didn’t, and that’s fine. Although they don’t get the attention, we learn as much (sometimes more) from negative studies as we do from positive ones. If we put people on every drug that initially showed promise for their conditions, my patients would have a pretty huge medication list. For Alzheimer’s disease alone I remember studies that once suggested ibuprofen, statins, estrogen, nicotine, and several vitamins might be effective (“might” being the key word). Today we’re looking at the PDE5 inhibitors and semaglutide. The jury is still out on them, but whichever way it goes we’ll still learn something.

The statins are good drugs. Their benefits in cardiac and cerebrovascular disease can’t be disputed (I’m sure someone would, but that’s not the point of this piece). But, like all drugs, they don’t work for everything.

Just like other sciences, everything we do now in medicine is based on both the successes and failures of what came before. We learn from both and keep moving forward.
 

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

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Erenumab Reduces Nonopioid Medication Overuse Headache in Chronic Migraine

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Tue, 10/15/2024 - 06:58

 

In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.

Dr. Stewart J. Tepper

Prior Studies Did Not Focus on MOH

Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.

Dr. Alan M. Rapoport

 

Phase 4, Randomized, Placebo-Controlled Trial

In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.

Investigators defined remission as either of the following through months 4-6:

  • < 10 mean monthly acute headache medication days per month (AHMD)
  • < 14 mean monthly headache days (MHD)

In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.

No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.

Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.

“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”

He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
 

 

 

Detox Versus No Detox

In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.

Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
 

Managing Chronic Migraine and MOH

Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.

In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.

Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.

Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.

Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”

Dr. Rapoport reports no relevant financial conflicts.

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In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.

Dr. Stewart J. Tepper

Prior Studies Did Not Focus on MOH

Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.

Dr. Alan M. Rapoport

 

Phase 4, Randomized, Placebo-Controlled Trial

In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.

Investigators defined remission as either of the following through months 4-6:

  • < 10 mean monthly acute headache medication days per month (AHMD)
  • < 14 mean monthly headache days (MHD)

In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.

No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.

Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.

“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”

He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
 

 

 

Detox Versus No Detox

In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.

Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
 

Managing Chronic Migraine and MOH

Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.

In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.

Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.

Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.

Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”

Dr. Rapoport reports no relevant financial conflicts.

 

In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.

Dr. Stewart J. Tepper

Prior Studies Did Not Focus on MOH

Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.

Dr. Alan M. Rapoport

 

Phase 4, Randomized, Placebo-Controlled Trial

In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.

Investigators defined remission as either of the following through months 4-6:

  • < 10 mean monthly acute headache medication days per month (AHMD)
  • < 14 mean monthly headache days (MHD)

In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.

No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.

Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.

“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”

He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
 

 

 

Detox Versus No Detox

In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.

Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
 

Managing Chronic Migraine and MOH

Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.

In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.

Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.

Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.

Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”

Dr. Rapoport reports no relevant financial conflicts.

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High Cadmium Level Associated With Cognitive Impairment Risk

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Changed
Fri, 10/04/2024 - 10:58

 

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

  • Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
  • Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
  • Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
  • Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
  • Mean follow-up was 10 years.

TAKEAWAY:

  • Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
  • High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
  • No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
  • Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

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

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TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

  • Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
  • Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
  • Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
  • Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
  • Mean follow-up was 10 years.

TAKEAWAY:

  • Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
  • High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
  • No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
  • Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

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

 

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

  • Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
  • Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
  • Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
  • Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
  • Mean follow-up was 10 years.

TAKEAWAY:

  • Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
  • High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
  • No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
  • Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

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

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Women Are Entering Higher-Paid MD Specialties at Higher Rates

Article Type
Changed
Fri, 10/04/2024 - 10:47

More women are enrolling into higher-paid physician specialty fields, especially surgery, but they still have a way to go before reaching parity with their male counterparts, an analysis found.

Rising Interest in Surgical Specialties

Among 490,188 students to “pipeline” specialties from 2008 to 2022 (47.4% women), the proportion of women entering higher-paid specialties grew from 32.7% to 40.8% (P = .003), powered by increased interest in surgical jobs, reported Karina Pereira-Lima, PhD, MSc, of the University of Michigan, Ann Arbor, Michigan, and colleagues in JAMA.

“It was exciting to see the proportion of women entering high-compensation surgical specialties jump from 28.8% in 2008 to 42.4% in 2022,” Dr. Pereira-Lima told this news organization. “At the same time, the proportion of women entering high-compensation nonsurgical specialties didn’t change much over time, and we even saw a decrease in female applicants to those fields.”

The researchers launched the analysis to better understand the career choices of medical students. “We’ve been seeing a national trend where more women are entering the medical profession, with women now making up more than half of medical school students. At the same time, most of the highest compensation specialties have traditionally been dominated by men,” Dr. Pereira-Lima said. “Tracking changes in the proportion of women entering these programs over time can give us insight into whether we’re making progress toward more equitable gender representation in these high-compensation specialties.”
 

Highest vs Lowest Compensated Specialties

The researchers analyzed 2008-2022 data from students and applicants to Accreditation Council for Graduate Medical Education–accredited residency programs in “pipeline” specialties, defined as those that lead to primary board certification.

Specialties defined as having the highest compensation, based on data from Doximity, were the surgical fields of neurosurgery, ophthalmology, orthopedic surgery, otorhinolaryngology, plastic surgery (integrated), surgery (general), thoracic surgery (integrated), urology, and vascular surgery (integrated) and the nonsurgical fields of anesthesiology, dermatology, nuclear medicine, radiation oncology, and radiology (diagnostic).

The lowest-compensated fields were all nonsurgical: Child neurology, emergency medicine, family medicine, internal medicine, internal medicine/pediatrics, medical genetics and genomics, neurology, nuclear medicine, obstetrics and gynecology, pathology, pediatrics, physical medicine and rehabilitation, and psychiatry.

The proportion of women entering lower-compensated specialties stayed steady from 2008 to 2022 (53.0% vs 53.3%, respectively; P = .44), as did the percentage entering nonsurgical specialties (37.6% vs 38.7%, respectively; P = .55).

Meanwhile, the proportion of women applicants to high-compensation nonsurgical specialties fell from 36.8% in 2009 to 34.3% in 2022 (P = .001), whereas the number grew in high-compensation surgical specialties from 28.1% in 2009 to 37.6% in 2022 (P < .001).
 

Implications for Future Representation

The findings suggest that “the issue of women’s underrepresentation isn’t just limited to surgical specialties,” Dr. Pereira-Lima said. “It’s affecting many of the highest-compensated specialties overall. Moving forward, it’ll be important to investigate what’s driving the increase in women entering these highly compensated surgical specialties and see if those same factors can be applied to other fields where women are still underrepresented.”

She added that it will take time for the dominance of women among medical students to translate into more representation in the physician workforce. Also, “studies show that female physicians have higher attrition rates than men. To achieve a more balanced gender representation in medicine, it’s crucial not just to have more women entering the profession, but to focus on addressing the barriers that hinder their career advancement.”

Shikha Jain, MD, University of Illinois College of Medicine, Chicago, an oncologist who’s studied gender representation in medicine, told this news organization that the rise in women entering surgical fields may be due to an increased focus on gender disparity. “It’s nice to see that we’re actually seeing some movement there,” she said, especially in light of findings that female surgeons have better outcomes than male surgeons.

However, research has shown that women in surgical specialties aren’t as highly compensated as men, she said. “Bullying, harassment, micro- and macro-aggressions, and gaslighting are all huge problems that continue to persist in healthcare. They’re a huge part of the reason many women weren’t in these specialties. With the increase in women entering these fields, I hope we see a real concerted effort to address these challenges so we can continue to see these trends moving forward.”

Dr. Pereira-Lima is supported by the National Institutes of Health, and another author is supported by the National Institute of Mental Health. No author disclosures were reported. Dr. Jain had no disclosures.
 

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

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More women are enrolling into higher-paid physician specialty fields, especially surgery, but they still have a way to go before reaching parity with their male counterparts, an analysis found.

Rising Interest in Surgical Specialties

Among 490,188 students to “pipeline” specialties from 2008 to 2022 (47.4% women), the proportion of women entering higher-paid specialties grew from 32.7% to 40.8% (P = .003), powered by increased interest in surgical jobs, reported Karina Pereira-Lima, PhD, MSc, of the University of Michigan, Ann Arbor, Michigan, and colleagues in JAMA.

“It was exciting to see the proportion of women entering high-compensation surgical specialties jump from 28.8% in 2008 to 42.4% in 2022,” Dr. Pereira-Lima told this news organization. “At the same time, the proportion of women entering high-compensation nonsurgical specialties didn’t change much over time, and we even saw a decrease in female applicants to those fields.”

The researchers launched the analysis to better understand the career choices of medical students. “We’ve been seeing a national trend where more women are entering the medical profession, with women now making up more than half of medical school students. At the same time, most of the highest compensation specialties have traditionally been dominated by men,” Dr. Pereira-Lima said. “Tracking changes in the proportion of women entering these programs over time can give us insight into whether we’re making progress toward more equitable gender representation in these high-compensation specialties.”
 

Highest vs Lowest Compensated Specialties

The researchers analyzed 2008-2022 data from students and applicants to Accreditation Council for Graduate Medical Education–accredited residency programs in “pipeline” specialties, defined as those that lead to primary board certification.

Specialties defined as having the highest compensation, based on data from Doximity, were the surgical fields of neurosurgery, ophthalmology, orthopedic surgery, otorhinolaryngology, plastic surgery (integrated), surgery (general), thoracic surgery (integrated), urology, and vascular surgery (integrated) and the nonsurgical fields of anesthesiology, dermatology, nuclear medicine, radiation oncology, and radiology (diagnostic).

The lowest-compensated fields were all nonsurgical: Child neurology, emergency medicine, family medicine, internal medicine, internal medicine/pediatrics, medical genetics and genomics, neurology, nuclear medicine, obstetrics and gynecology, pathology, pediatrics, physical medicine and rehabilitation, and psychiatry.

The proportion of women entering lower-compensated specialties stayed steady from 2008 to 2022 (53.0% vs 53.3%, respectively; P = .44), as did the percentage entering nonsurgical specialties (37.6% vs 38.7%, respectively; P = .55).

Meanwhile, the proportion of women applicants to high-compensation nonsurgical specialties fell from 36.8% in 2009 to 34.3% in 2022 (P = .001), whereas the number grew in high-compensation surgical specialties from 28.1% in 2009 to 37.6% in 2022 (P < .001).
 

Implications for Future Representation

The findings suggest that “the issue of women’s underrepresentation isn’t just limited to surgical specialties,” Dr. Pereira-Lima said. “It’s affecting many of the highest-compensated specialties overall. Moving forward, it’ll be important to investigate what’s driving the increase in women entering these highly compensated surgical specialties and see if those same factors can be applied to other fields where women are still underrepresented.”

She added that it will take time for the dominance of women among medical students to translate into more representation in the physician workforce. Also, “studies show that female physicians have higher attrition rates than men. To achieve a more balanced gender representation in medicine, it’s crucial not just to have more women entering the profession, but to focus on addressing the barriers that hinder their career advancement.”

Shikha Jain, MD, University of Illinois College of Medicine, Chicago, an oncologist who’s studied gender representation in medicine, told this news organization that the rise in women entering surgical fields may be due to an increased focus on gender disparity. “It’s nice to see that we’re actually seeing some movement there,” she said, especially in light of findings that female surgeons have better outcomes than male surgeons.

However, research has shown that women in surgical specialties aren’t as highly compensated as men, she said. “Bullying, harassment, micro- and macro-aggressions, and gaslighting are all huge problems that continue to persist in healthcare. They’re a huge part of the reason many women weren’t in these specialties. With the increase in women entering these fields, I hope we see a real concerted effort to address these challenges so we can continue to see these trends moving forward.”

Dr. Pereira-Lima is supported by the National Institutes of Health, and another author is supported by the National Institute of Mental Health. No author disclosures were reported. Dr. Jain had no disclosures.
 

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

More women are enrolling into higher-paid physician specialty fields, especially surgery, but they still have a way to go before reaching parity with their male counterparts, an analysis found.

Rising Interest in Surgical Specialties

Among 490,188 students to “pipeline” specialties from 2008 to 2022 (47.4% women), the proportion of women entering higher-paid specialties grew from 32.7% to 40.8% (P = .003), powered by increased interest in surgical jobs, reported Karina Pereira-Lima, PhD, MSc, of the University of Michigan, Ann Arbor, Michigan, and colleagues in JAMA.

“It was exciting to see the proportion of women entering high-compensation surgical specialties jump from 28.8% in 2008 to 42.4% in 2022,” Dr. Pereira-Lima told this news organization. “At the same time, the proportion of women entering high-compensation nonsurgical specialties didn’t change much over time, and we even saw a decrease in female applicants to those fields.”

The researchers launched the analysis to better understand the career choices of medical students. “We’ve been seeing a national trend where more women are entering the medical profession, with women now making up more than half of medical school students. At the same time, most of the highest compensation specialties have traditionally been dominated by men,” Dr. Pereira-Lima said. “Tracking changes in the proportion of women entering these programs over time can give us insight into whether we’re making progress toward more equitable gender representation in these high-compensation specialties.”
 

Highest vs Lowest Compensated Specialties

The researchers analyzed 2008-2022 data from students and applicants to Accreditation Council for Graduate Medical Education–accredited residency programs in “pipeline” specialties, defined as those that lead to primary board certification.

Specialties defined as having the highest compensation, based on data from Doximity, were the surgical fields of neurosurgery, ophthalmology, orthopedic surgery, otorhinolaryngology, plastic surgery (integrated), surgery (general), thoracic surgery (integrated), urology, and vascular surgery (integrated) and the nonsurgical fields of anesthesiology, dermatology, nuclear medicine, radiation oncology, and radiology (diagnostic).

The lowest-compensated fields were all nonsurgical: Child neurology, emergency medicine, family medicine, internal medicine, internal medicine/pediatrics, medical genetics and genomics, neurology, nuclear medicine, obstetrics and gynecology, pathology, pediatrics, physical medicine and rehabilitation, and psychiatry.

The proportion of women entering lower-compensated specialties stayed steady from 2008 to 2022 (53.0% vs 53.3%, respectively; P = .44), as did the percentage entering nonsurgical specialties (37.6% vs 38.7%, respectively; P = .55).

Meanwhile, the proportion of women applicants to high-compensation nonsurgical specialties fell from 36.8% in 2009 to 34.3% in 2022 (P = .001), whereas the number grew in high-compensation surgical specialties from 28.1% in 2009 to 37.6% in 2022 (P < .001).
 

Implications for Future Representation

The findings suggest that “the issue of women’s underrepresentation isn’t just limited to surgical specialties,” Dr. Pereira-Lima said. “It’s affecting many of the highest-compensated specialties overall. Moving forward, it’ll be important to investigate what’s driving the increase in women entering these highly compensated surgical specialties and see if those same factors can be applied to other fields where women are still underrepresented.”

She added that it will take time for the dominance of women among medical students to translate into more representation in the physician workforce. Also, “studies show that female physicians have higher attrition rates than men. To achieve a more balanced gender representation in medicine, it’s crucial not just to have more women entering the profession, but to focus on addressing the barriers that hinder their career advancement.”

Shikha Jain, MD, University of Illinois College of Medicine, Chicago, an oncologist who’s studied gender representation in medicine, told this news organization that the rise in women entering surgical fields may be due to an increased focus on gender disparity. “It’s nice to see that we’re actually seeing some movement there,” she said, especially in light of findings that female surgeons have better outcomes than male surgeons.

However, research has shown that women in surgical specialties aren’t as highly compensated as men, she said. “Bullying, harassment, micro- and macro-aggressions, and gaslighting are all huge problems that continue to persist in healthcare. They’re a huge part of the reason many women weren’t in these specialties. With the increase in women entering these fields, I hope we see a real concerted effort to address these challenges so we can continue to see these trends moving forward.”

Dr. Pereira-Lima is supported by the National Institutes of Health, and another author is supported by the National Institute of Mental Health. No author disclosures were reported. Dr. Jain had no disclosures.
 

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

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sNFl and sGFAP Predict MS Disability in Unique Ways

Article Type
Changed
Thu, 10/03/2024 - 16:10

Serum glial fibrillary acidic protein (sGFAP) is quickly maturing as a biomarker to predict disability in patients with multiple sclerosis (MS), but it will add information to, not compete with, serum neurofilament light chain (sNFl) levels, according to multiple independent studies.

The basic consensus is that “elevated sNFl levels predict inflammatory-associated worsening, while sGFAP values correlate with progression independent of inflammation,” said Enric Monreal, MD, Immunology Department, Ramón y Cajal University Hospital, Madrid, Spain.

This key message was repeated by several researchers presenting data at the 2024 ECTRIMS 2004 meeting, including one delivered as a latebreaker. There was also general agreement that sGFAP will eventually be a routine prognostic tool even if more data are needed to validate how it will be used in routine MS management.
 

A New Biomarker for MS Disability Progression

Although apparently reliable for predicting MS disability, “sGFAP is about 5 years behind where we are with sNFl,” said Evan Madill, MD, a clinical research fellow at the Brigham Multiple Sclerosis Research Center, Harvard Medical School, Boston. He does think, however, that it is coming to clinical practice.

In the study he presented, 744 patients from the Brigham MS Research Center database were evaluated retrospectively for sGFAP levels and subsequent disability progression. Among this cohort, for which sGFAP levels were collected at baseline and over time, 46.5% had 6-month confirmed disability progression (CDP) over follow-up.

On univariate analysis, sGFAP levels correlated with and predicted CDP, need for a new ambulatory aid, and conversion to secondary progressive MS (SPMS). For patients less than 60 years of age, all of these correlations were highly significant (P ≤ .002). On multivariate analysis, the significance was preserved for CDP (P = .032) and for need of a new ambulatory aid (P = .007), but it was lost for SPMS conversion.

Notably, his data suggest that a one-time baseline measurement of sGFAP was more useful than change in sGFAP as a predictor.

It is unclear why sGFAP is less predictive in older individuals, but Dr. Madill speculated that non-MS phenomena might play a role at older ages. Treatment did not influence sGFAP levels in this study, but Dr. Madill said most of the data were collected before anti-CD20 monoclonal antibodies were widely available.

The observational study data presented by Dr. Monreal involved 725 patients drawn from 13 European hospitals. sGFAP and sNFl levels were evaluated from blood drawn within 12 months of MS onset. Over time these biomarkers had overlapping but different predictive strengths.

Consistent with previously published studies, which link elevations in sNFl to neuronal damage and elevations in sGFAP to astrogliosis, sGFAP was found to be more useful for predicting progression independent of relapse activity (PIRA), particularly in patients with low sNFl levels.

Increases in sNFl were associated with an increased risk of both PIRA and relapse-associated worsening (RAW), but sNFl was more closely associated with RAW in untreated patients. The risk of PIRA and RAW were similar across GFAP and sNFl levels in those patients treated with high-efficacy disease-modifying therapies (DMT).

Overall, when stratifying the cohort into three groups, those with both low sNFl and low GFAP, those with high sNFl with low GFAP, and those with high GFAP and low sNFl, the relative risks of disability associated with PIRA and RAW diverged, suggesting these biomarkers correlate with different processes of progression.
 

 

 

Comparing sGFAP and sNFl

This same principle was explored further in the latebreaking presentation by Ahmed Abdelhak, MD, a clinical instructor, Weill Institute for Neurosciences, University of California, San Francisco. The objective of his study was to compare sGFAP and sNFl for predicting PIRA in patients on treatment.

The study included 212 patients from the Swiss Multiple Sclerosis Cohort who were started on fingolimod or on B-cell depleting therapies like rituximab. After correcting for sex, age at onset, baseline Expanded Disability Status Scale (EDSS) scores, and other variables, Dr. Abdelhak also reported that the predictive values for PIRA were different for sGFAP relative to sNFl at least on the group level.

However, in this study, unlike the analysis of the Brigham MS Research Center data, changes in sGFAP over time when on treatment did have prognostic value, and there was a relationship between sGFAP levels and treatment. Although reductions in GFAP predicted less disability progression whether patients were treated with fingolimod B-cell depleting therapies, that patterns were different. Dr. Abdelhak, like the other investigators speaking at ECTRIMS, also said the data so far favor sGFAP over sNFl for predicting PIRA.

Each z-score unit change in sGFAP corresponded to a 47% lower risk of PIRA in follow-up over 6.8 years, Dr. Abdelhak reported, adding that the predictive value of sGFAP was “numerically stronger than the corresponding relation for sNFl.”

So far, clinical utility of sGFAP remains speculative. Most of the correlations he presented were on a group rather than the individual level. Moreover, Dr. Abdelhak cautioned that these correlations, based on observational data, do not necessarily reflect causation.

Nonetheless, remarking on the parallels of his data on sGFAP and sNFl with other studies presented at the ECTRIMS meeting, Dr. Abdelhak foresees a time when GFAP will be a prognostic tool, offering relative simplicity and lower cost than the current standard of imaging. He also sees a role in clinical research.

“Monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide insights valuable for design and interpretation of trial outcomes,” he said.

Dr. Monreal reported financial relationships with Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Dr. Madill and Dr. Abdelhak reported no potential conflicts of interest.

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Serum glial fibrillary acidic protein (sGFAP) is quickly maturing as a biomarker to predict disability in patients with multiple sclerosis (MS), but it will add information to, not compete with, serum neurofilament light chain (sNFl) levels, according to multiple independent studies.

The basic consensus is that “elevated sNFl levels predict inflammatory-associated worsening, while sGFAP values correlate with progression independent of inflammation,” said Enric Monreal, MD, Immunology Department, Ramón y Cajal University Hospital, Madrid, Spain.

This key message was repeated by several researchers presenting data at the 2024 ECTRIMS 2004 meeting, including one delivered as a latebreaker. There was also general agreement that sGFAP will eventually be a routine prognostic tool even if more data are needed to validate how it will be used in routine MS management.
 

A New Biomarker for MS Disability Progression

Although apparently reliable for predicting MS disability, “sGFAP is about 5 years behind where we are with sNFl,” said Evan Madill, MD, a clinical research fellow at the Brigham Multiple Sclerosis Research Center, Harvard Medical School, Boston. He does think, however, that it is coming to clinical practice.

In the study he presented, 744 patients from the Brigham MS Research Center database were evaluated retrospectively for sGFAP levels and subsequent disability progression. Among this cohort, for which sGFAP levels were collected at baseline and over time, 46.5% had 6-month confirmed disability progression (CDP) over follow-up.

On univariate analysis, sGFAP levels correlated with and predicted CDP, need for a new ambulatory aid, and conversion to secondary progressive MS (SPMS). For patients less than 60 years of age, all of these correlations were highly significant (P ≤ .002). On multivariate analysis, the significance was preserved for CDP (P = .032) and for need of a new ambulatory aid (P = .007), but it was lost for SPMS conversion.

Notably, his data suggest that a one-time baseline measurement of sGFAP was more useful than change in sGFAP as a predictor.

It is unclear why sGFAP is less predictive in older individuals, but Dr. Madill speculated that non-MS phenomena might play a role at older ages. Treatment did not influence sGFAP levels in this study, but Dr. Madill said most of the data were collected before anti-CD20 monoclonal antibodies were widely available.

The observational study data presented by Dr. Monreal involved 725 patients drawn from 13 European hospitals. sGFAP and sNFl levels were evaluated from blood drawn within 12 months of MS onset. Over time these biomarkers had overlapping but different predictive strengths.

Consistent with previously published studies, which link elevations in sNFl to neuronal damage and elevations in sGFAP to astrogliosis, sGFAP was found to be more useful for predicting progression independent of relapse activity (PIRA), particularly in patients with low sNFl levels.

Increases in sNFl were associated with an increased risk of both PIRA and relapse-associated worsening (RAW), but sNFl was more closely associated with RAW in untreated patients. The risk of PIRA and RAW were similar across GFAP and sNFl levels in those patients treated with high-efficacy disease-modifying therapies (DMT).

Overall, when stratifying the cohort into three groups, those with both low sNFl and low GFAP, those with high sNFl with low GFAP, and those with high GFAP and low sNFl, the relative risks of disability associated with PIRA and RAW diverged, suggesting these biomarkers correlate with different processes of progression.
 

 

 

Comparing sGFAP and sNFl

This same principle was explored further in the latebreaking presentation by Ahmed Abdelhak, MD, a clinical instructor, Weill Institute for Neurosciences, University of California, San Francisco. The objective of his study was to compare sGFAP and sNFl for predicting PIRA in patients on treatment.

The study included 212 patients from the Swiss Multiple Sclerosis Cohort who were started on fingolimod or on B-cell depleting therapies like rituximab. After correcting for sex, age at onset, baseline Expanded Disability Status Scale (EDSS) scores, and other variables, Dr. Abdelhak also reported that the predictive values for PIRA were different for sGFAP relative to sNFl at least on the group level.

However, in this study, unlike the analysis of the Brigham MS Research Center data, changes in sGFAP over time when on treatment did have prognostic value, and there was a relationship between sGFAP levels and treatment. Although reductions in GFAP predicted less disability progression whether patients were treated with fingolimod B-cell depleting therapies, that patterns were different. Dr. Abdelhak, like the other investigators speaking at ECTRIMS, also said the data so far favor sGFAP over sNFl for predicting PIRA.

Each z-score unit change in sGFAP corresponded to a 47% lower risk of PIRA in follow-up over 6.8 years, Dr. Abdelhak reported, adding that the predictive value of sGFAP was “numerically stronger than the corresponding relation for sNFl.”

So far, clinical utility of sGFAP remains speculative. Most of the correlations he presented were on a group rather than the individual level. Moreover, Dr. Abdelhak cautioned that these correlations, based on observational data, do not necessarily reflect causation.

Nonetheless, remarking on the parallels of his data on sGFAP and sNFl with other studies presented at the ECTRIMS meeting, Dr. Abdelhak foresees a time when GFAP will be a prognostic tool, offering relative simplicity and lower cost than the current standard of imaging. He also sees a role in clinical research.

“Monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide insights valuable for design and interpretation of trial outcomes,” he said.

Dr. Monreal reported financial relationships with Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Dr. Madill and Dr. Abdelhak reported no potential conflicts of interest.

Serum glial fibrillary acidic protein (sGFAP) is quickly maturing as a biomarker to predict disability in patients with multiple sclerosis (MS), but it will add information to, not compete with, serum neurofilament light chain (sNFl) levels, according to multiple independent studies.

The basic consensus is that “elevated sNFl levels predict inflammatory-associated worsening, while sGFAP values correlate with progression independent of inflammation,” said Enric Monreal, MD, Immunology Department, Ramón y Cajal University Hospital, Madrid, Spain.

This key message was repeated by several researchers presenting data at the 2024 ECTRIMS 2004 meeting, including one delivered as a latebreaker. There was also general agreement that sGFAP will eventually be a routine prognostic tool even if more data are needed to validate how it will be used in routine MS management.
 

A New Biomarker for MS Disability Progression

Although apparently reliable for predicting MS disability, “sGFAP is about 5 years behind where we are with sNFl,” said Evan Madill, MD, a clinical research fellow at the Brigham Multiple Sclerosis Research Center, Harvard Medical School, Boston. He does think, however, that it is coming to clinical practice.

In the study he presented, 744 patients from the Brigham MS Research Center database were evaluated retrospectively for sGFAP levels and subsequent disability progression. Among this cohort, for which sGFAP levels were collected at baseline and over time, 46.5% had 6-month confirmed disability progression (CDP) over follow-up.

On univariate analysis, sGFAP levels correlated with and predicted CDP, need for a new ambulatory aid, and conversion to secondary progressive MS (SPMS). For patients less than 60 years of age, all of these correlations were highly significant (P ≤ .002). On multivariate analysis, the significance was preserved for CDP (P = .032) and for need of a new ambulatory aid (P = .007), but it was lost for SPMS conversion.

Notably, his data suggest that a one-time baseline measurement of sGFAP was more useful than change in sGFAP as a predictor.

It is unclear why sGFAP is less predictive in older individuals, but Dr. Madill speculated that non-MS phenomena might play a role at older ages. Treatment did not influence sGFAP levels in this study, but Dr. Madill said most of the data were collected before anti-CD20 monoclonal antibodies were widely available.

The observational study data presented by Dr. Monreal involved 725 patients drawn from 13 European hospitals. sGFAP and sNFl levels were evaluated from blood drawn within 12 months of MS onset. Over time these biomarkers had overlapping but different predictive strengths.

Consistent with previously published studies, which link elevations in sNFl to neuronal damage and elevations in sGFAP to astrogliosis, sGFAP was found to be more useful for predicting progression independent of relapse activity (PIRA), particularly in patients with low sNFl levels.

Increases in sNFl were associated with an increased risk of both PIRA and relapse-associated worsening (RAW), but sNFl was more closely associated with RAW in untreated patients. The risk of PIRA and RAW were similar across GFAP and sNFl levels in those patients treated with high-efficacy disease-modifying therapies (DMT).

Overall, when stratifying the cohort into three groups, those with both low sNFl and low GFAP, those with high sNFl with low GFAP, and those with high GFAP and low sNFl, the relative risks of disability associated with PIRA and RAW diverged, suggesting these biomarkers correlate with different processes of progression.
 

 

 

Comparing sGFAP and sNFl

This same principle was explored further in the latebreaking presentation by Ahmed Abdelhak, MD, a clinical instructor, Weill Institute for Neurosciences, University of California, San Francisco. The objective of his study was to compare sGFAP and sNFl for predicting PIRA in patients on treatment.

The study included 212 patients from the Swiss Multiple Sclerosis Cohort who were started on fingolimod or on B-cell depleting therapies like rituximab. After correcting for sex, age at onset, baseline Expanded Disability Status Scale (EDSS) scores, and other variables, Dr. Abdelhak also reported that the predictive values for PIRA were different for sGFAP relative to sNFl at least on the group level.

However, in this study, unlike the analysis of the Brigham MS Research Center data, changes in sGFAP over time when on treatment did have prognostic value, and there was a relationship between sGFAP levels and treatment. Although reductions in GFAP predicted less disability progression whether patients were treated with fingolimod B-cell depleting therapies, that patterns were different. Dr. Abdelhak, like the other investigators speaking at ECTRIMS, also said the data so far favor sGFAP over sNFl for predicting PIRA.

Each z-score unit change in sGFAP corresponded to a 47% lower risk of PIRA in follow-up over 6.8 years, Dr. Abdelhak reported, adding that the predictive value of sGFAP was “numerically stronger than the corresponding relation for sNFl.”

So far, clinical utility of sGFAP remains speculative. Most of the correlations he presented were on a group rather than the individual level. Moreover, Dr. Abdelhak cautioned that these correlations, based on observational data, do not necessarily reflect causation.

Nonetheless, remarking on the parallels of his data on sGFAP and sNFl with other studies presented at the ECTRIMS meeting, Dr. Abdelhak foresees a time when GFAP will be a prognostic tool, offering relative simplicity and lower cost than the current standard of imaging. He also sees a role in clinical research.

“Monitoring of sGFAP dynamics following DMT initiation could be used to prognosticate long-term PIRA risk and provide insights valuable for design and interpretation of trial outcomes,” he said.

Dr. Monreal reported financial relationships with Almirall, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Dr. Madill and Dr. Abdelhak reported no potential conflicts of interest.

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Autonomy Versus Safety in Cognitive Impairment Decision-Making

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Thu, 10/03/2024 - 11:47

– As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

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– As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

– As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

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Millennial Clinicians Face Pay Disparities by Specialty, Other Factors

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Thu, 10/03/2024 - 11:41

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

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Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

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Time to Revisit the Standard Treatment Approach in Children With MS?

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Wed, 10/02/2024 - 15:34

Growing evidence supports the use of highly effective disease-modifying therapies for children with multiple sclerosis (MS). However, only few of these medications are licensed for pediatric use, indicating it may be time to reconsider the standard treatment approach for this patient population.

Treatments for pediatric-onset MS have mostly been used off-label until the recent approvals of fingolimod, dimethyl fumarate, and teriflunomide. Typically, children with MS start with moderately effective therapies, while more potent options are reserved for those who don’t respond.

However, recent research suggests this may not be the most effective treatment strategy for this patient population. Several studies suggesting impressive treatment responses to highly effective therapies (HETs) in children were presented at the 2024 ECTRIMS annual meeting.

In one study, initiating monoclonal antibody treatment during childhood was associated with reduced disability into early adulthood and beyond.

“Our findings are a strong argument for rethinking current treatment guidelines,” said study investigator Sifat Sharmin, PhD, The University of Melbourne, Australia.

“By allowing earlier access to highly effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she added.

In another presentation, Yael Hacohen, MD, Great Ormond Street Hospital, London, England, noted that the use of these more effective monoclonal antibody therapies in children with MS has been associated with some improvements in Expanded Disability Status Scale (EDSS) scores after 2 or 3 years of treatment.

Maybe this is a sign that “this is a population that can repair, in contrast to adult patients,” she wondered.

MS is primarily a disease of adults, but pediatric MS accounts for up to 5% of all cases. Children with MS tend to have much more active disease than adults, Dr. Hacohen explained. However, they also tend to recover from attacks more quickly with little disability, which sometimes causes diagnostic delays.

A pediatrician or family doctor will often dismiss pins and needles or blurred vision that only lasts a couple of days and won’t send the patient for an MRI, she said. But on MRI, pediatric patients with MS often have multiple lesions, even though they may have had very few symptoms. The EDSS may not change very much, but there can still be significant brain atrophy.

Over the past 20 years, there’s been an explosion of new disease-modifying treatments for MS, but these high-efficacy treatments, such as antibody therapies, are often not prescribed until the patient reaches the age of 18 years, both Dr. Sharmin and Dr. Hacohen pointed out.

“We need to get some of these medications approved for use in children,” Dr. Hacohen said.
 

Slowed Disability

In her presentation, Dr. Sharmin reported an observational study that included 282 patients younger than 18 years at MS onset identified from the French MS Registry, the Italian MS Register, and the Global MSBase Registry.

Of these, 110 (39%) had initiated therapy with ocrelizumab, rituximab, or natalizumab early in the disease course between ages 12 and 17 years and 172 (61%) had initiated treatment with one of these agents at ages 20-22 years.

The primary outcome was the difference in EDSS scores from baseline (at age 18 years) to ages 23-27 years between those who had started treatment with one of these agents early and those who had started late.

At the baseline of age 18 years, the median EDSS score was 1.5 in the early group and 1.3 in the late group. Median follow-up time was 10.8 years.

The data were adjusted for baseline differences in factors such as sex, age at symptom onset, time from onset to clinically definite MS, and the number of relapses (using inverse probability treatment weighting based on propensity scores).

Results showed that between ages 23 and 27 years, disability was a 0.57 step lower in the early group than in the late group. The mean absolute differences in EDSS from baseline were 0.40 in the early group and 0.95 in the late group. This benefit of early treatment persisted throughout the rest of the follow-up period.

The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%, Dr. Sharmin noted.

“Starting these highly effective therapies, before the onset of significant neurological impairments, appears crucial for preserving neurological function in children with relapsing-remitting MS over the long term,” she said.

These findings highlight the critical importance of early intervention in pediatric-onset MS, she concluded.

The researchers are planning further work to generate more evidence to support the proactive treatment of pediatric-onset MS, with a particular focus on assessing the long-term risks for immunosuppressive therapies in this population.
 

 

 

Ocrelizumab Experience in Children

Dr. Hacohen reported on a UK cohort of children with MS treated with ocrelizumab, with 66 patients having more than 12 months of follow-up. Of these, only four patients had relapses, and there was no evidence of disease activity in 94% patients.

“We’ve stopped doing relapse clinic because they really don’t relapse,” Dr. Hacohen reported.

“This has completely changed our practice in pediatric MS,” she said. Twice a year, patients come in to have pre-infusion bloods and clinical assessments and then return a month later for treatment.

“They only have to come to the hospital for 4 days a year, and the rest of the time, they can forget they have MS,” said Dr. Hacohen.

In terms of complications, one patient in the UK cohort developed enterovirus meningitis but recovered completely, and two patients had hypogammaglobulinemia and were changed to an extended interval or to a different agent.

Dr. Hacohen cautioned that hypogammaglobulinemia — a condition in which immunoglobulin levels are below normal — is “something that hypothetically we should maybe be more worried about in the pediatric population, particularly as these patients are more likely to be on anti-CD20 therapies for a much longer time.”

She said this complication tends to happen after about 4 or 5 years of treatment. “If we start seeing IgG levels dropping, we need to come up with a plan about extending the dosing interval. We need clinical trials to look at this.”

Dr. Hacohen also drew attention to the issue of vaccinations not being effective in patients on anti-CD20 antibody therapy, which could be a particular problem in children.

However, given that vaccinations do seem to be effective in patients taking natalizumab, pediatric patients with highly active disease could receive the drug for 3-6 months while receiving vaccines and then switched over to ocrelizumab, she said.

Giving natalizumab for such a short period is not believed to have a high risk of developing JCV antibodies, she added.

In another presentation, Brenda Banwell, MD, Johns Hopkins Children’s Center, Baltimore, reported new data from an early study (OPERETTA 1) with ocrelizumab in pediatric relapsing-remitting MS showing a safety profile similar to that observed in adults. The suggested dose is 300 mg for children under 35 kg and 600 mg for adults over 35 kg, administered every 24 weeks. These doses will be further investigated in the ongoing phase III OPERETTA 2 trial.

Dr. Sharmin received a postdoctoral fellowship from MS Australia. The OPERETTA studies were sponsored by F. Hoffmann-La Roche. Dr. Banwell served as a consultant to Roche. Dr. Hacohen reported no relevant disclosures.
 

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

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Growing evidence supports the use of highly effective disease-modifying therapies for children with multiple sclerosis (MS). However, only few of these medications are licensed for pediatric use, indicating it may be time to reconsider the standard treatment approach for this patient population.

Treatments for pediatric-onset MS have mostly been used off-label until the recent approvals of fingolimod, dimethyl fumarate, and teriflunomide. Typically, children with MS start with moderately effective therapies, while more potent options are reserved for those who don’t respond.

However, recent research suggests this may not be the most effective treatment strategy for this patient population. Several studies suggesting impressive treatment responses to highly effective therapies (HETs) in children were presented at the 2024 ECTRIMS annual meeting.

In one study, initiating monoclonal antibody treatment during childhood was associated with reduced disability into early adulthood and beyond.

“Our findings are a strong argument for rethinking current treatment guidelines,” said study investigator Sifat Sharmin, PhD, The University of Melbourne, Australia.

“By allowing earlier access to highly effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she added.

In another presentation, Yael Hacohen, MD, Great Ormond Street Hospital, London, England, noted that the use of these more effective monoclonal antibody therapies in children with MS has been associated with some improvements in Expanded Disability Status Scale (EDSS) scores after 2 or 3 years of treatment.

Maybe this is a sign that “this is a population that can repair, in contrast to adult patients,” she wondered.

MS is primarily a disease of adults, but pediatric MS accounts for up to 5% of all cases. Children with MS tend to have much more active disease than adults, Dr. Hacohen explained. However, they also tend to recover from attacks more quickly with little disability, which sometimes causes diagnostic delays.

A pediatrician or family doctor will often dismiss pins and needles or blurred vision that only lasts a couple of days and won’t send the patient for an MRI, she said. But on MRI, pediatric patients with MS often have multiple lesions, even though they may have had very few symptoms. The EDSS may not change very much, but there can still be significant brain atrophy.

Over the past 20 years, there’s been an explosion of new disease-modifying treatments for MS, but these high-efficacy treatments, such as antibody therapies, are often not prescribed until the patient reaches the age of 18 years, both Dr. Sharmin and Dr. Hacohen pointed out.

“We need to get some of these medications approved for use in children,” Dr. Hacohen said.
 

Slowed Disability

In her presentation, Dr. Sharmin reported an observational study that included 282 patients younger than 18 years at MS onset identified from the French MS Registry, the Italian MS Register, and the Global MSBase Registry.

Of these, 110 (39%) had initiated therapy with ocrelizumab, rituximab, or natalizumab early in the disease course between ages 12 and 17 years and 172 (61%) had initiated treatment with one of these agents at ages 20-22 years.

The primary outcome was the difference in EDSS scores from baseline (at age 18 years) to ages 23-27 years between those who had started treatment with one of these agents early and those who had started late.

At the baseline of age 18 years, the median EDSS score was 1.5 in the early group and 1.3 in the late group. Median follow-up time was 10.8 years.

The data were adjusted for baseline differences in factors such as sex, age at symptom onset, time from onset to clinically definite MS, and the number of relapses (using inverse probability treatment weighting based on propensity scores).

Results showed that between ages 23 and 27 years, disability was a 0.57 step lower in the early group than in the late group. The mean absolute differences in EDSS from baseline were 0.40 in the early group and 0.95 in the late group. This benefit of early treatment persisted throughout the rest of the follow-up period.

The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%, Dr. Sharmin noted.

“Starting these highly effective therapies, before the onset of significant neurological impairments, appears crucial for preserving neurological function in children with relapsing-remitting MS over the long term,” she said.

These findings highlight the critical importance of early intervention in pediatric-onset MS, she concluded.

The researchers are planning further work to generate more evidence to support the proactive treatment of pediatric-onset MS, with a particular focus on assessing the long-term risks for immunosuppressive therapies in this population.
 

 

 

Ocrelizumab Experience in Children

Dr. Hacohen reported on a UK cohort of children with MS treated with ocrelizumab, with 66 patients having more than 12 months of follow-up. Of these, only four patients had relapses, and there was no evidence of disease activity in 94% patients.

“We’ve stopped doing relapse clinic because they really don’t relapse,” Dr. Hacohen reported.

“This has completely changed our practice in pediatric MS,” she said. Twice a year, patients come in to have pre-infusion bloods and clinical assessments and then return a month later for treatment.

“They only have to come to the hospital for 4 days a year, and the rest of the time, they can forget they have MS,” said Dr. Hacohen.

In terms of complications, one patient in the UK cohort developed enterovirus meningitis but recovered completely, and two patients had hypogammaglobulinemia and were changed to an extended interval or to a different agent.

Dr. Hacohen cautioned that hypogammaglobulinemia — a condition in which immunoglobulin levels are below normal — is “something that hypothetically we should maybe be more worried about in the pediatric population, particularly as these patients are more likely to be on anti-CD20 therapies for a much longer time.”

She said this complication tends to happen after about 4 or 5 years of treatment. “If we start seeing IgG levels dropping, we need to come up with a plan about extending the dosing interval. We need clinical trials to look at this.”

Dr. Hacohen also drew attention to the issue of vaccinations not being effective in patients on anti-CD20 antibody therapy, which could be a particular problem in children.

However, given that vaccinations do seem to be effective in patients taking natalizumab, pediatric patients with highly active disease could receive the drug for 3-6 months while receiving vaccines and then switched over to ocrelizumab, she said.

Giving natalizumab for such a short period is not believed to have a high risk of developing JCV antibodies, she added.

In another presentation, Brenda Banwell, MD, Johns Hopkins Children’s Center, Baltimore, reported new data from an early study (OPERETTA 1) with ocrelizumab in pediatric relapsing-remitting MS showing a safety profile similar to that observed in adults. The suggested dose is 300 mg for children under 35 kg and 600 mg for adults over 35 kg, administered every 24 weeks. These doses will be further investigated in the ongoing phase III OPERETTA 2 trial.

Dr. Sharmin received a postdoctoral fellowship from MS Australia. The OPERETTA studies were sponsored by F. Hoffmann-La Roche. Dr. Banwell served as a consultant to Roche. Dr. Hacohen reported no relevant disclosures.
 

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

Growing evidence supports the use of highly effective disease-modifying therapies for children with multiple sclerosis (MS). However, only few of these medications are licensed for pediatric use, indicating it may be time to reconsider the standard treatment approach for this patient population.

Treatments for pediatric-onset MS have mostly been used off-label until the recent approvals of fingolimod, dimethyl fumarate, and teriflunomide. Typically, children with MS start with moderately effective therapies, while more potent options are reserved for those who don’t respond.

However, recent research suggests this may not be the most effective treatment strategy for this patient population. Several studies suggesting impressive treatment responses to highly effective therapies (HETs) in children were presented at the 2024 ECTRIMS annual meeting.

In one study, initiating monoclonal antibody treatment during childhood was associated with reduced disability into early adulthood and beyond.

“Our findings are a strong argument for rethinking current treatment guidelines,” said study investigator Sifat Sharmin, PhD, The University of Melbourne, Australia.

“By allowing earlier access to highly effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she added.

In another presentation, Yael Hacohen, MD, Great Ormond Street Hospital, London, England, noted that the use of these more effective monoclonal antibody therapies in children with MS has been associated with some improvements in Expanded Disability Status Scale (EDSS) scores after 2 or 3 years of treatment.

Maybe this is a sign that “this is a population that can repair, in contrast to adult patients,” she wondered.

MS is primarily a disease of adults, but pediatric MS accounts for up to 5% of all cases. Children with MS tend to have much more active disease than adults, Dr. Hacohen explained. However, they also tend to recover from attacks more quickly with little disability, which sometimes causes diagnostic delays.

A pediatrician or family doctor will often dismiss pins and needles or blurred vision that only lasts a couple of days and won’t send the patient for an MRI, she said. But on MRI, pediatric patients with MS often have multiple lesions, even though they may have had very few symptoms. The EDSS may not change very much, but there can still be significant brain atrophy.

Over the past 20 years, there’s been an explosion of new disease-modifying treatments for MS, but these high-efficacy treatments, such as antibody therapies, are often not prescribed until the patient reaches the age of 18 years, both Dr. Sharmin and Dr. Hacohen pointed out.

“We need to get some of these medications approved for use in children,” Dr. Hacohen said.
 

Slowed Disability

In her presentation, Dr. Sharmin reported an observational study that included 282 patients younger than 18 years at MS onset identified from the French MS Registry, the Italian MS Register, and the Global MSBase Registry.

Of these, 110 (39%) had initiated therapy with ocrelizumab, rituximab, or natalizumab early in the disease course between ages 12 and 17 years and 172 (61%) had initiated treatment with one of these agents at ages 20-22 years.

The primary outcome was the difference in EDSS scores from baseline (at age 18 years) to ages 23-27 years between those who had started treatment with one of these agents early and those who had started late.

At the baseline of age 18 years, the median EDSS score was 1.5 in the early group and 1.3 in the late group. Median follow-up time was 10.8 years.

The data were adjusted for baseline differences in factors such as sex, age at symptom onset, time from onset to clinically definite MS, and the number of relapses (using inverse probability treatment weighting based on propensity scores).

Results showed that between ages 23 and 27 years, disability was a 0.57 step lower in the early group than in the late group. The mean absolute differences in EDSS from baseline were 0.40 in the early group and 0.95 in the late group. This benefit of early treatment persisted throughout the rest of the follow-up period.

The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%, Dr. Sharmin noted.

“Starting these highly effective therapies, before the onset of significant neurological impairments, appears crucial for preserving neurological function in children with relapsing-remitting MS over the long term,” she said.

These findings highlight the critical importance of early intervention in pediatric-onset MS, she concluded.

The researchers are planning further work to generate more evidence to support the proactive treatment of pediatric-onset MS, with a particular focus on assessing the long-term risks for immunosuppressive therapies in this population.
 

 

 

Ocrelizumab Experience in Children

Dr. Hacohen reported on a UK cohort of children with MS treated with ocrelizumab, with 66 patients having more than 12 months of follow-up. Of these, only four patients had relapses, and there was no evidence of disease activity in 94% patients.

“We’ve stopped doing relapse clinic because they really don’t relapse,” Dr. Hacohen reported.

“This has completely changed our practice in pediatric MS,” she said. Twice a year, patients come in to have pre-infusion bloods and clinical assessments and then return a month later for treatment.

“They only have to come to the hospital for 4 days a year, and the rest of the time, they can forget they have MS,” said Dr. Hacohen.

In terms of complications, one patient in the UK cohort developed enterovirus meningitis but recovered completely, and two patients had hypogammaglobulinemia and were changed to an extended interval or to a different agent.

Dr. Hacohen cautioned that hypogammaglobulinemia — a condition in which immunoglobulin levels are below normal — is “something that hypothetically we should maybe be more worried about in the pediatric population, particularly as these patients are more likely to be on anti-CD20 therapies for a much longer time.”

She said this complication tends to happen after about 4 or 5 years of treatment. “If we start seeing IgG levels dropping, we need to come up with a plan about extending the dosing interval. We need clinical trials to look at this.”

Dr. Hacohen also drew attention to the issue of vaccinations not being effective in patients on anti-CD20 antibody therapy, which could be a particular problem in children.

However, given that vaccinations do seem to be effective in patients taking natalizumab, pediatric patients with highly active disease could receive the drug for 3-6 months while receiving vaccines and then switched over to ocrelizumab, she said.

Giving natalizumab for such a short period is not believed to have a high risk of developing JCV antibodies, she added.

In another presentation, Brenda Banwell, MD, Johns Hopkins Children’s Center, Baltimore, reported new data from an early study (OPERETTA 1) with ocrelizumab in pediatric relapsing-remitting MS showing a safety profile similar to that observed in adults. The suggested dose is 300 mg for children under 35 kg and 600 mg for adults over 35 kg, administered every 24 weeks. These doses will be further investigated in the ongoing phase III OPERETTA 2 trial.

Dr. Sharmin received a postdoctoral fellowship from MS Australia. The OPERETTA studies were sponsored by F. Hoffmann-La Roche. Dr. Banwell served as a consultant to Roche. Dr. Hacohen reported no relevant disclosures.
 

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

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