Randy Dotinga

SAVANNAH, GEORGIA — A new clinical education tool aims to speed the diagnosis of amyotrophic lateral sclerosis (ALS), which often goes undetected for months even in neurologist offices.

The one-page “thinkALS” tool, designed for clinicians who don’t specialize in neuromuscular disorders, offers a guide to recognize ALS symptoms and determine when it’s time to refer patients to ALS clinics.

“Time is of the essence. It’s really important because the paradigm of looking at ALS is shifting from this being a fatal disease that nobody can do anything about,” said Suma Babu, MBBS, MPH, assistant professor of neurology at Massachusetts General Hospital/Harvard Medical School in Boston, in a presentation at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. “As a community, we need to think about how can get to the diagnosis point early and get patients started on therapies.”
 

On Average, ALS Diagnosis Takes 12-15 Months

As Babu noted, the percentage of patients initially diagnosed with something else may be as high as 52%. The time to diagnosis in ALS remained steady at a mean 12-15 months from 1996-1998 to 2000-2018.

“If you keep in mind that an average ALS patient lives only 3-5 years from symptom onset, they’re spending one third of their survival time in just trying to figure out what the diagnosis is,” Babu said. “Often, they may even undergo unnecessary testing and unnecessary surgeries — carpal tunnel releases, spinal surgeries, and so on.”

Babu’s own research, which is under review for publication, examined 2011-2021 Medicare claims to determine the typical time from first neurologist consult to confirmed ALS diagnosis. The mean for ALS/neuromuscular specialists is 9.6 months, while it’s 16.7 months for nonspecialist neurologists.

“It’s a hard pill to swallow,” Babu said, referring to the fact that neurologists are contributing to some of this situation. “But it is a challenge because ALS does not have a definitive diagnostic test, and you’re ruling out other possibilities.”
 

A ‘Sense of Nihilism’ About Prognoses

She added that “unless you’re seeing a lot of ALS patients, this is not going to be on a neurologist’s or a nurse practitioner’s radar to think about ALS early and then refer them to the right place.”

There’s also an unwarranted “sense of nihilism” about prognoses for patients, she said. “Sometimes people do not understand what’s going on within the ALS field in terms of ‘What are we going to do about it if it’s diagnosed?’ ”

The new one-page tool will be helpful in making diagnoses, she said. “If you have a patient who has asymmetric, progressive weakness, there is an instrument you can turn to that will walk you through the most common symptoms. It’ll also walk you through what to do next.”

The tool lists features of ALS and factors that support — or don’t support — an ALS diagnosis. Users are told to “think ALS” if features in two categories are present and no features in a third category are present.
 

Referral Wording Is Crucial

Babu added that the “important key feature of this instrument” is guidance for non-neurologists regarding what to write on a referral to neurology so the patient is channeled directly to an ALS clinic. The recommended wording: “CLINICAL SUSPICION FOR ALS.”

Neurologist Ximena Arcila-Londono, MD, of Henry Ford Health in Detroit, spoke after Babu’s presentation and agreed that wording is crucial in referrals. “Please include in your words ‘Rule out motor neuron disorder’ or ‘Rule out ALS,’ ” she said. “Some people in the community are very reluctant to use those words in their referral. If you don’t use the referral and you send them [regarding] weakness, that person is going to get stuck in the general neurology pile. The moment you use the word ‘motor neuron disorder’ or ALS, most of us will get to those patients within a month.”

The tool’s wording adds that “most ALS centers can accommodate urgent ALS referrals within 2 weeks.”

Babu disclosed receiving research funding from the AANEM Foundation, American Academy of Neurology, Muscular Dystrophy Association, OrphAI, Biogen, Ionis, Novartis, Denali, uniQure, and MarvelBiome. Arcila-Londono had no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — A new clinical education tool aims to speed the diagnosis of amyotrophic lateral sclerosis (ALS), which often goes undetected for months even in neurologist offices.

The one-page “thinkALS” tool, designed for clinicians who don’t specialize in neuromuscular disorders, offers a guide to recognize ALS symptoms and determine when it’s time to refer patients to ALS clinics.

“Time is of the essence. It’s really important because the paradigm of looking at ALS is shifting from this being a fatal disease that nobody can do anything about,” said Suma Babu, MBBS, MPH, assistant professor of neurology at Massachusetts General Hospital/Harvard Medical School in Boston, in a presentation at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. “As a community, we need to think about how can get to the diagnosis point early and get patients started on therapies.”
 

On Average, ALS Diagnosis Takes 12-15 Months

As Babu noted, the percentage of patients initially diagnosed with something else may be as high as 52%. The time to diagnosis in ALS remained steady at a mean 12-15 months from 1996-1998 to 2000-2018.

“If you keep in mind that an average ALS patient lives only 3-5 years from symptom onset, they’re spending one third of their survival time in just trying to figure out what the diagnosis is,” Babu said. “Often, they may even undergo unnecessary testing and unnecessary surgeries — carpal tunnel releases, spinal surgeries, and so on.”

Babu’s own research, which is under review for publication, examined 2011-2021 Medicare claims to determine the typical time from first neurologist consult to confirmed ALS diagnosis. The mean for ALS/neuromuscular specialists is 9.6 months, while it’s 16.7 months for nonspecialist neurologists.

“It’s a hard pill to swallow,” Babu said, referring to the fact that neurologists are contributing to some of this situation. “But it is a challenge because ALS does not have a definitive diagnostic test, and you’re ruling out other possibilities.”
 

A ‘Sense of Nihilism’ About Prognoses

She added that “unless you’re seeing a lot of ALS patients, this is not going to be on a neurologist’s or a nurse practitioner’s radar to think about ALS early and then refer them to the right place.”

There’s also an unwarranted “sense of nihilism” about prognoses for patients, she said. “Sometimes people do not understand what’s going on within the ALS field in terms of ‘What are we going to do about it if it’s diagnosed?’ ”

The new one-page tool will be helpful in making diagnoses, she said. “If you have a patient who has asymmetric, progressive weakness, there is an instrument you can turn to that will walk you through the most common symptoms. It’ll also walk you through what to do next.”

The tool lists features of ALS and factors that support — or don’t support — an ALS diagnosis. Users are told to “think ALS” if features in two categories are present and no features in a third category are present.
 

Referral Wording Is Crucial

Babu added that the “important key feature of this instrument” is guidance for non-neurologists regarding what to write on a referral to neurology so the patient is channeled directly to an ALS clinic. The recommended wording: “CLINICAL SUSPICION FOR ALS.”

Neurologist Ximena Arcila-Londono, MD, of Henry Ford Health in Detroit, spoke after Babu’s presentation and agreed that wording is crucial in referrals. “Please include in your words ‘Rule out motor neuron disorder’ or ‘Rule out ALS,’ ” she said. “Some people in the community are very reluctant to use those words in their referral. If you don’t use the referral and you send them [regarding] weakness, that person is going to get stuck in the general neurology pile. The moment you use the word ‘motor neuron disorder’ or ALS, most of us will get to those patients within a month.”

The tool’s wording adds that “most ALS centers can accommodate urgent ALS referrals within 2 weeks.”

Babu disclosed receiving research funding from the AANEM Foundation, American Academy of Neurology, Muscular Dystrophy Association, OrphAI, Biogen, Ionis, Novartis, Denali, uniQure, and MarvelBiome. Arcila-Londono had no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — A new clinical education tool aims to speed the diagnosis of amyotrophic lateral sclerosis (ALS), which often goes undetected for months even in neurologist offices.

The one-page “thinkALS” tool, designed for clinicians who don’t specialize in neuromuscular disorders, offers a guide to recognize ALS symptoms and determine when it’s time to refer patients to ALS clinics.

“Time is of the essence. It’s really important because the paradigm of looking at ALS is shifting from this being a fatal disease that nobody can do anything about,” said Suma Babu, MBBS, MPH, assistant professor of neurology at Massachusetts General Hospital/Harvard Medical School in Boston, in a presentation at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. “As a community, we need to think about how can get to the diagnosis point early and get patients started on therapies.”
 

On Average, ALS Diagnosis Takes 12-15 Months

As Babu noted, the percentage of patients initially diagnosed with something else may be as high as 52%. The time to diagnosis in ALS remained steady at a mean 12-15 months from 1996-1998 to 2000-2018.

“If you keep in mind that an average ALS patient lives only 3-5 years from symptom onset, they’re spending one third of their survival time in just trying to figure out what the diagnosis is,” Babu said. “Often, they may even undergo unnecessary testing and unnecessary surgeries — carpal tunnel releases, spinal surgeries, and so on.”

Babu’s own research, which is under review for publication, examined 2011-2021 Medicare claims to determine the typical time from first neurologist consult to confirmed ALS diagnosis. The mean for ALS/neuromuscular specialists is 9.6 months, while it’s 16.7 months for nonspecialist neurologists.

“It’s a hard pill to swallow,” Babu said, referring to the fact that neurologists are contributing to some of this situation. “But it is a challenge because ALS does not have a definitive diagnostic test, and you’re ruling out other possibilities.”
 

A ‘Sense of Nihilism’ About Prognoses

She added that “unless you’re seeing a lot of ALS patients, this is not going to be on a neurologist’s or a nurse practitioner’s radar to think about ALS early and then refer them to the right place.”

There’s also an unwarranted “sense of nihilism” about prognoses for patients, she said. “Sometimes people do not understand what’s going on within the ALS field in terms of ‘What are we going to do about it if it’s diagnosed?’ ”

The new one-page tool will be helpful in making diagnoses, she said. “If you have a patient who has asymmetric, progressive weakness, there is an instrument you can turn to that will walk you through the most common symptoms. It’ll also walk you through what to do next.”

The tool lists features of ALS and factors that support — or don’t support — an ALS diagnosis. Users are told to “think ALS” if features in two categories are present and no features in a third category are present.
 

Referral Wording Is Crucial

Babu added that the “important key feature of this instrument” is guidance for non-neurologists regarding what to write on a referral to neurology so the patient is channeled directly to an ALS clinic. The recommended wording: “CLINICAL SUSPICION FOR ALS.”

Neurologist Ximena Arcila-Londono, MD, of Henry Ford Health in Detroit, spoke after Babu’s presentation and agreed that wording is crucial in referrals. “Please include in your words ‘Rule out motor neuron disorder’ or ‘Rule out ALS,’ ” she said. “Some people in the community are very reluctant to use those words in their referral. If you don’t use the referral and you send them [regarding] weakness, that person is going to get stuck in the general neurology pile. The moment you use the word ‘motor neuron disorder’ or ALS, most of us will get to those patients within a month.”

The tool’s wording adds that “most ALS centers can accommodate urgent ALS referrals within 2 weeks.”

Babu disclosed receiving research funding from the AANEM Foundation, American Academy of Neurology, Muscular Dystrophy Association, OrphAI, Biogen, Ionis, Novartis, Denali, uniQure, and MarvelBiome. Arcila-Londono had no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Heart problems are common in the vast majority of neuromuscular disorders, and cardiac monitoring of patients is crucial, even at younger ages, a neurologist told an audience of nerve/muscle specialists.

The cardiac conditions can range from asymptomatic to potentially lethal, Nicholas J. Silvestri, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York, said in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. “It’s really important to know when to do tests and refer to cardiology, and it’s really important to find a cardiologist who can work in concert in taking care of these patients.”
 

Protein Alterations May Disrupt Heart Muscles

In muscular dystrophies, a prevailing theory suggests that alterations to proteins such as dystrophin disrupt structural integrity in both muscle and cardiac cells, he said.

In Duchenne muscular dystrophy (DMD), cardiomyopathy, cardiac conduction abnormalities, or both usually appear in patients by age 10. “It’s important to know that it’s probably present to some degree before that, and it’s not going to get better over time,” he said.

Cardiac problems are universal in DMD by age 18, he said. “Men and boys are living longer, so they have the opportunity to develop the cardiac abnormalities that accrue with time.” Conduction abnormalities typically appear first. “In a lot of these boys, you’ll typically see persistent sinus tachycardia. But they can also develop atrial arrhythmias and bundle branch blocks.”

Sudden cardiac death is responsible for mortality in an estimated 15% patients with DMD. “Very sadly, I lost a patient this way just a few months ago,” Silvestri said.
 

ECGs and Echos Are Recommended

Screening is crucial. “Make sure that patients get that referral and get these tests done,” he said. “You need an ECG and echo by diagnosis or age 6. This is usually repeated annually or biannually, typically by the cardiologist you’re working with.”

The good news is that there’s evidence of survival benefits from treatment with angiotensin-converting enzyme inhibitors for dilated cardiomyopathy. “Some cardiac experts feel treatment with angiotensin receptor blockers (ARBs) is equivalent.”

Most boys will get echocardiograms, he said, “but there’s a lot of evidence showing that cardiac MRI is probably preferable for a number of reasons,” including better visualization. But the need for sedation limits access, he said, and cardiac MRI may not be available at some facilities.
 

Worse Outcomes in Becker Muscular Dystrophy (BMD)

Cardiac involvement is more common and more severe in BMD than in DMD. About 50% of deaths in BMD are attributed to malignant arrhythmias or congestive heart failure, he said.

Screening requirements and treatment options in BMD are similar to those in DMD, with the added option of heart transplantation.

Silvestri cautioned that up to 40% of female carriers of dystrophin mutations can develop cardiac dysfunction similar to that seen in DMD and BMD. Cardiac assessments are recommended every 5 years. “It’s important to genotype Mom,” he said, especially in light of the fact that two thirds of DMD cases may be inherited.

“When I send genetic testing on the mother and find her to be a carrier, I send her to a cardiologist so she has the appropriate screening done,” he said.
 

Pacemakers May Be Considered in Type 1 Myotonic Dystrophy

In type 1 myotonic dystrophy, cardiac conduction abnormalities are seen in two thirds of patients, and sudden cardiac death in up to 30% of patients. “When it is diagnosed, patients do need an ECG at that time, as well as annually,” he said.

Holter monitoring or implantable loop recorders may be recommended, and permanent pacing via an implantable cardioverter-defibrillator might be appropriate.

“Based on the literature to date, the exact timing is not is not clear,” Silvestri said. “The electrophysiologists in my area tend to be very aggressive, thankfully, and treat them fairly soon with pacemakers when we see the first sign of trouble.”

Silvestri disclosed consultant/advisory relationships with argenx, Alexion, Amgen, UCB, Immunovant, and Janssen.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Heart problems are common in the vast majority of neuromuscular disorders, and cardiac monitoring of patients is crucial, even at younger ages, a neurologist told an audience of nerve/muscle specialists.

The cardiac conditions can range from asymptomatic to potentially lethal, Nicholas J. Silvestri, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York, said in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. “It’s really important to know when to do tests and refer to cardiology, and it’s really important to find a cardiologist who can work in concert in taking care of these patients.”
 

Protein Alterations May Disrupt Heart Muscles

In muscular dystrophies, a prevailing theory suggests that alterations to proteins such as dystrophin disrupt structural integrity in both muscle and cardiac cells, he said.

In Duchenne muscular dystrophy (DMD), cardiomyopathy, cardiac conduction abnormalities, or both usually appear in patients by age 10. “It’s important to know that it’s probably present to some degree before that, and it’s not going to get better over time,” he said.

Cardiac problems are universal in DMD by age 18, he said. “Men and boys are living longer, so they have the opportunity to develop the cardiac abnormalities that accrue with time.” Conduction abnormalities typically appear first. “In a lot of these boys, you’ll typically see persistent sinus tachycardia. But they can also develop atrial arrhythmias and bundle branch blocks.”

Sudden cardiac death is responsible for mortality in an estimated 15% patients with DMD. “Very sadly, I lost a patient this way just a few months ago,” Silvestri said.
 

ECGs and Echos Are Recommended

Screening is crucial. “Make sure that patients get that referral and get these tests done,” he said. “You need an ECG and echo by diagnosis or age 6. This is usually repeated annually or biannually, typically by the cardiologist you’re working with.”

The good news is that there’s evidence of survival benefits from treatment with angiotensin-converting enzyme inhibitors for dilated cardiomyopathy. “Some cardiac experts feel treatment with angiotensin receptor blockers (ARBs) is equivalent.”

Most boys will get echocardiograms, he said, “but there’s a lot of evidence showing that cardiac MRI is probably preferable for a number of reasons,” including better visualization. But the need for sedation limits access, he said, and cardiac MRI may not be available at some facilities.
 

Worse Outcomes in Becker Muscular Dystrophy (BMD)

Cardiac involvement is more common and more severe in BMD than in DMD. About 50% of deaths in BMD are attributed to malignant arrhythmias or congestive heart failure, he said.

Screening requirements and treatment options in BMD are similar to those in DMD, with the added option of heart transplantation.

Silvestri cautioned that up to 40% of female carriers of dystrophin mutations can develop cardiac dysfunction similar to that seen in DMD and BMD. Cardiac assessments are recommended every 5 years. “It’s important to genotype Mom,” he said, especially in light of the fact that two thirds of DMD cases may be inherited.

“When I send genetic testing on the mother and find her to be a carrier, I send her to a cardiologist so she has the appropriate screening done,” he said.
 

Pacemakers May Be Considered in Type 1 Myotonic Dystrophy

In type 1 myotonic dystrophy, cardiac conduction abnormalities are seen in two thirds of patients, and sudden cardiac death in up to 30% of patients. “When it is diagnosed, patients do need an ECG at that time, as well as annually,” he said.

Holter monitoring or implantable loop recorders may be recommended, and permanent pacing via an implantable cardioverter-defibrillator might be appropriate.

“Based on the literature to date, the exact timing is not is not clear,” Silvestri said. “The electrophysiologists in my area tend to be very aggressive, thankfully, and treat them fairly soon with pacemakers when we see the first sign of trouble.”

Silvestri disclosed consultant/advisory relationships with argenx, Alexion, Amgen, UCB, Immunovant, and Janssen.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Heart problems are common in the vast majority of neuromuscular disorders, and cardiac monitoring of patients is crucial, even at younger ages, a neurologist told an audience of nerve/muscle specialists.

The cardiac conditions can range from asymptomatic to potentially lethal, Nicholas J. Silvestri, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York, said in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. “It’s really important to know when to do tests and refer to cardiology, and it’s really important to find a cardiologist who can work in concert in taking care of these patients.”
 

Protein Alterations May Disrupt Heart Muscles

In muscular dystrophies, a prevailing theory suggests that alterations to proteins such as dystrophin disrupt structural integrity in both muscle and cardiac cells, he said.

In Duchenne muscular dystrophy (DMD), cardiomyopathy, cardiac conduction abnormalities, or both usually appear in patients by age 10. “It’s important to know that it’s probably present to some degree before that, and it’s not going to get better over time,” he said.

Cardiac problems are universal in DMD by age 18, he said. “Men and boys are living longer, so they have the opportunity to develop the cardiac abnormalities that accrue with time.” Conduction abnormalities typically appear first. “In a lot of these boys, you’ll typically see persistent sinus tachycardia. But they can also develop atrial arrhythmias and bundle branch blocks.”

Sudden cardiac death is responsible for mortality in an estimated 15% patients with DMD. “Very sadly, I lost a patient this way just a few months ago,” Silvestri said.
 

ECGs and Echos Are Recommended

Screening is crucial. “Make sure that patients get that referral and get these tests done,” he said. “You need an ECG and echo by diagnosis or age 6. This is usually repeated annually or biannually, typically by the cardiologist you’re working with.”

The good news is that there’s evidence of survival benefits from treatment with angiotensin-converting enzyme inhibitors for dilated cardiomyopathy. “Some cardiac experts feel treatment with angiotensin receptor blockers (ARBs) is equivalent.”

Most boys will get echocardiograms, he said, “but there’s a lot of evidence showing that cardiac MRI is probably preferable for a number of reasons,” including better visualization. But the need for sedation limits access, he said, and cardiac MRI may not be available at some facilities.
 

Worse Outcomes in Becker Muscular Dystrophy (BMD)

Cardiac involvement is more common and more severe in BMD than in DMD. About 50% of deaths in BMD are attributed to malignant arrhythmias or congestive heart failure, he said.

Screening requirements and treatment options in BMD are similar to those in DMD, with the added option of heart transplantation.

Silvestri cautioned that up to 40% of female carriers of dystrophin mutations can develop cardiac dysfunction similar to that seen in DMD and BMD. Cardiac assessments are recommended every 5 years. “It’s important to genotype Mom,” he said, especially in light of the fact that two thirds of DMD cases may be inherited.

“When I send genetic testing on the mother and find her to be a carrier, I send her to a cardiologist so she has the appropriate screening done,” he said.
 

Pacemakers May Be Considered in Type 1 Myotonic Dystrophy

In type 1 myotonic dystrophy, cardiac conduction abnormalities are seen in two thirds of patients, and sudden cardiac death in up to 30% of patients. “When it is diagnosed, patients do need an ECG at that time, as well as annually,” he said.

Holter monitoring or implantable loop recorders may be recommended, and permanent pacing via an implantable cardioverter-defibrillator might be appropriate.

“Based on the literature to date, the exact timing is not is not clear,” Silvestri said. “The electrophysiologists in my area tend to be very aggressive, thankfully, and treat them fairly soon with pacemakers when we see the first sign of trouble.”

Silvestri disclosed consultant/advisory relationships with argenx, Alexion, Amgen, UCB, Immunovant, and Janssen.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Current disease-modifying therapies for amyotrophic lateral sclerosis (ALS) don’t extend lifespans by much, but several drug options are available, nerve specialists learned.

The glutamate blocker riluzole (Rilutek), which became the first ALS drug to receive US Food and Drug Administration (FDA) approval in 1995, continues to be used, Michael D. Weiss, MD, professor of neurology at University of Washington School of Medicine, Seattle, said in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

Weiss highlighted a 2012 Cochrane Library review that examined research and found the drug is “reasonably safe” and prolongs median survival by about 2-3 months. “About 12% develop liver disease. It’s pretty rare that we stop the medicine due to liver toxicity.”
 

Earlier Treatment Could Pay Dividends

A recent study “suggests we might be able to get more bang for our buck from riluzole” by initiating treatment earlier, Weiss said.

Researchers tracked 4778 patients with ALS, including 3446 (72.1%) who took riluzole. Those who took the drug survived a median 2 extra months (22.6 vs 20.2 months; P < .001). The data suggested that delaying riluzole initiation by 1 year (from 6 months to 18 months after diagnosis) reduced the median survival by 1.9 months (from 40.1 to 38.2 months).

There’s “a relatively significant additional benefit” to earlier treatment, Weiss said, although patients will vary on whether they think it’s meaningful. As for limitations, “there’s no clear impact on disease progression, and there’s a need for periodic monitoring of liver function profile.” 

He added that there’s an out-of-pocket co-pay. “Even as a generic, it’s not that cheap. Depending on the source, it could cost anywhere from $1800 to $8400 a year.”
 

Edaravone Could Lack Relevant Benefit

No other ALS treatment appeared until 2017, when the FDA approved the novel antioxidant edaravone (Radicava). In 2022, the agency approved an oral suspension version, but a study published that year suggested there may not be a clinically relevant benefit.

The University of Washington, where Weiss works, offered the drug to 144 patients, according to an analysis. Eighty percent of the patients wanted it, but insurers refused to cover it for more than 20%. The average time to treatment with the drug was 28 days after patients said they wanted it.

That’s a “substantial delay,” Weiss said.

The cost is about $171,000 a year, he said, and assistance is limited for underinsured patients.*

Other Options

As Weiss noted, another drug, AMX0035 (Relyvrio), received FDA approval in 2022, but its manufacturer pulled it from the US/Canada market in April 2024 following poor phase 3 trial findings.

In 2023, the FDA approved another drug, the antisense oligonucleotide tofersen (Qalsody), in patients with ALS associated with a mutation in the superoxide dismutase 1 gene. According to the FDA, reductions in plasma neurofilament light concentration were “reasonably likely to predict a clinical benefit in patients.”

Only 1%-2% of patients with ALS fit the criteria to get the drug, Weiss said. He noted other limitations such as the cost ($180,000 a year), the need for lifelong monthly intrathecal injections, and serious neurological side effects in 7% of patients per a 2022 trial.

Weiss disclosed advisory board (Alexion, Ra [now UCB], argenx, Biogen, Mitsubishi Tanabe Pharma, Amylyx), data safety monitoring board (Sanofi, AI), consulting (Cytokinetics, CSL Behring), and speaker (Soleo) relationships.

*Correction, 10/23/2024: This story originally quoted Weiss as saying the maker of edaravone provides no assistance to underinsured patients. Weiss has clarified that he should have said this coverage is “limited.”

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Current disease-modifying therapies for amyotrophic lateral sclerosis (ALS) don’t extend lifespans by much, but several drug options are available, nerve specialists learned.

The glutamate blocker riluzole (Rilutek), which became the first ALS drug to receive US Food and Drug Administration (FDA) approval in 1995, continues to be used, Michael D. Weiss, MD, professor of neurology at University of Washington School of Medicine, Seattle, said in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

Weiss highlighted a 2012 Cochrane Library review that examined research and found the drug is “reasonably safe” and prolongs median survival by about 2-3 months. “About 12% develop liver disease. It’s pretty rare that we stop the medicine due to liver toxicity.”
 

Earlier Treatment Could Pay Dividends

A recent study “suggests we might be able to get more bang for our buck from riluzole” by initiating treatment earlier, Weiss said.

Researchers tracked 4778 patients with ALS, including 3446 (72.1%) who took riluzole. Those who took the drug survived a median 2 extra months (22.6 vs 20.2 months; P < .001). The data suggested that delaying riluzole initiation by 1 year (from 6 months to 18 months after diagnosis) reduced the median survival by 1.9 months (from 40.1 to 38.2 months).

There’s “a relatively significant additional benefit” to earlier treatment, Weiss said, although patients will vary on whether they think it’s meaningful. As for limitations, “there’s no clear impact on disease progression, and there’s a need for periodic monitoring of liver function profile.” 

He added that there’s an out-of-pocket co-pay. “Even as a generic, it’s not that cheap. Depending on the source, it could cost anywhere from $1800 to $8400 a year.”
 

Edaravone Could Lack Relevant Benefit

No other ALS treatment appeared until 2017, when the FDA approved the novel antioxidant edaravone (Radicava). In 2022, the agency approved an oral suspension version, but a study published that year suggested there may not be a clinically relevant benefit.

The University of Washington, where Weiss works, offered the drug to 144 patients, according to an analysis. Eighty percent of the patients wanted it, but insurers refused to cover it for more than 20%. The average time to treatment with the drug was 28 days after patients said they wanted it.

That’s a “substantial delay,” Weiss said.

The cost is about $171,000 a year, he said, and assistance is limited for underinsured patients.*

Other Options

As Weiss noted, another drug, AMX0035 (Relyvrio), received FDA approval in 2022, but its manufacturer pulled it from the US/Canada market in April 2024 following poor phase 3 trial findings.

In 2023, the FDA approved another drug, the antisense oligonucleotide tofersen (Qalsody), in patients with ALS associated with a mutation in the superoxide dismutase 1 gene. According to the FDA, reductions in plasma neurofilament light concentration were “reasonably likely to predict a clinical benefit in patients.”

Only 1%-2% of patients with ALS fit the criteria to get the drug, Weiss said. He noted other limitations such as the cost ($180,000 a year), the need for lifelong monthly intrathecal injections, and serious neurological side effects in 7% of patients per a 2022 trial.

Weiss disclosed advisory board (Alexion, Ra [now UCB], argenx, Biogen, Mitsubishi Tanabe Pharma, Amylyx), data safety monitoring board (Sanofi, AI), consulting (Cytokinetics, CSL Behring), and speaker (Soleo) relationships.

*Correction, 10/23/2024: This story originally quoted Weiss as saying the maker of edaravone provides no assistance to underinsured patients. Weiss has clarified that he should have said this coverage is “limited.”

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Current disease-modifying therapies for amyotrophic lateral sclerosis (ALS) don’t extend lifespans by much, but several drug options are available, nerve specialists learned.

The glutamate blocker riluzole (Rilutek), which became the first ALS drug to receive US Food and Drug Administration (FDA) approval in 1995, continues to be used, Michael D. Weiss, MD, professor of neurology at University of Washington School of Medicine, Seattle, said in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

Weiss highlighted a 2012 Cochrane Library review that examined research and found the drug is “reasonably safe” and prolongs median survival by about 2-3 months. “About 12% develop liver disease. It’s pretty rare that we stop the medicine due to liver toxicity.”
 

Earlier Treatment Could Pay Dividends

A recent study “suggests we might be able to get more bang for our buck from riluzole” by initiating treatment earlier, Weiss said.

Researchers tracked 4778 patients with ALS, including 3446 (72.1%) who took riluzole. Those who took the drug survived a median 2 extra months (22.6 vs 20.2 months; P < .001). The data suggested that delaying riluzole initiation by 1 year (from 6 months to 18 months after diagnosis) reduced the median survival by 1.9 months (from 40.1 to 38.2 months).

There’s “a relatively significant additional benefit” to earlier treatment, Weiss said, although patients will vary on whether they think it’s meaningful. As for limitations, “there’s no clear impact on disease progression, and there’s a need for periodic monitoring of liver function profile.” 

He added that there’s an out-of-pocket co-pay. “Even as a generic, it’s not that cheap. Depending on the source, it could cost anywhere from $1800 to $8400 a year.”
 

Edaravone Could Lack Relevant Benefit

No other ALS treatment appeared until 2017, when the FDA approved the novel antioxidant edaravone (Radicava). In 2022, the agency approved an oral suspension version, but a study published that year suggested there may not be a clinically relevant benefit.

The University of Washington, where Weiss works, offered the drug to 144 patients, according to an analysis. Eighty percent of the patients wanted it, but insurers refused to cover it for more than 20%. The average time to treatment with the drug was 28 days after patients said they wanted it.

That’s a “substantial delay,” Weiss said.

The cost is about $171,000 a year, he said, and assistance is limited for underinsured patients.*

Other Options

As Weiss noted, another drug, AMX0035 (Relyvrio), received FDA approval in 2022, but its manufacturer pulled it from the US/Canada market in April 2024 following poor phase 3 trial findings.

In 2023, the FDA approved another drug, the antisense oligonucleotide tofersen (Qalsody), in patients with ALS associated with a mutation in the superoxide dismutase 1 gene. According to the FDA, reductions in plasma neurofilament light concentration were “reasonably likely to predict a clinical benefit in patients.”

Only 1%-2% of patients with ALS fit the criteria to get the drug, Weiss said. He noted other limitations such as the cost ($180,000 a year), the need for lifelong monthly intrathecal injections, and serious neurological side effects in 7% of patients per a 2022 trial.

Weiss disclosed advisory board (Alexion, Ra [now UCB], argenx, Biogen, Mitsubishi Tanabe Pharma, Amylyx), data safety monitoring board (Sanofi, AI), consulting (Cytokinetics, CSL Behring), and speaker (Soleo) relationships.

*Correction, 10/23/2024: This story originally quoted Weiss as saying the maker of edaravone provides no assistance to underinsured patients. Weiss has clarified that he should have said this coverage is “limited.”

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — One patient with autoimmune myasthenia gravis (MG) has a niece with the same diagnosis, and at least one of his other close relatives may have it too. Another patient with MG lost his father and brother to complications from the disease, while a surviving brother also has it. These two cases, reported at a meeting of nerve/muscle specialists, spotlight one of the mysteries of MG: What role does heredity play in this disorder?

“Clinical familial associations — when transmission appears to be vertical, from parent to offspring — suggest that there is much yet to learn about genetic bases for autoimmunity and how certain mutations could favor selection for specific immune disorders,” said Elena Shanina, MD, PhD, a neurology professor at the University of Texas Medical Branch, Galveston, in an interview. She and colleagues presented the two case reports at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

As Shanina noted, MG is usually sporadic without a link to heredity. However, she said, research suggests that up to 7% of patients have MG in their family history.

“There are well-described genetic causes for congenital myasthenic syndromes, in which mutations occur in genes for neuromuscular junction (NMJ) proteins affecting NMJ function. However, much less is known about genetic associations to autoimmune MG,” she said.

“More than a decade ago, differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides were suggested to suffice in producing MG, and specific HLA DQ susceptibility links were found predisposing to MG. More recent studies have tried to identify specific genes such as CTLA4 mutations that enhance autoimmunity and neuroinflammation.”
 

Two Cases

In one of the case reports, a 75-year-old White man with hereditary coagulopathy presented with myasthenic crisis in the setting of acute pulmonary embolism. Chronic symptoms included diplopia, ptosis, and proximal muscle weakness.

A niece of the patient has been diagnosed with MG and suffers from ocular symptoms. Meanwhile, an uncle has ptosis but no diagnosis yet, and a daughter has dermatomyositis. Like MG, dermatomyositis is an autoimmune disease that causes muscle weakness.

The patient, who’s CTLA4 negative, is faring well on eculizumab after failing standard therapies, Shanina said.

In the other case, a 67-year-old Hispanic man presented with diplopia, generalized fatigue, and weakness. Like the other patient, he was seropositive for acetylcholine receptor antibodies.

This patient lost his father and brother to complications from MG. Another brother, who’s still living, also has MG.

“The patient has minimal manifestation status with disease and is currently controlled using oral immunomodulatory therapies,” Shanina said. “He is also CTLA4 negative.”
 

Genetics and Environment May Each Play a Role

Shanina called for research exploring mutations and inheritance patterns in families with MG.

“If there are genetic causes that increase autoimmunity with specific propensity for certain immune diseases, correcting those mutations could fundamentally change how we treat — and prevent — at least some autoimmune diseases,” she said. “For example, if HLA linkage is directly involved in determining susceptibility to MG, and if the presence of a specific HLA locus allele is sufficient to produce disease, HLA gene editing could be a future therapy to prevent such diseases. Likewise, monoclonal antibodies that target products of genes that increase risk for autoimmunity might be able to reduce such risks without modifying the patient’s genome.”

Henry J. Kaminski, MD, professor of neurology at George Washington University, Washington, DC, is familiar with the report’s findings. In an interview, he noted that while genetic profiles can make MG more likely, “the situation is not like Huntington’s or Alzheimer’s where there is a strong genetic risk.” 

Instead, he said, there’s “a genetic risk coupled to some environmental stimulus that leads to the development of MG, which is true for many complex autoimmune conditions.” 

While he doesn’t think the two new case reports are especially noteworthy, Kaminski said “the ability to assess genetic risk factors across patients will elucidate understanding of MG. Personalized medicine choices will likely require understanding of genetic risks.”

While understanding MG in families is “always good to know from a research perspective,” there’s no reason to launch surveillance of relatives to see if they also have the disease, he said.

Also, Kaminski cautioned that it’s important to differentiate autoimmune MG from congenital myasthenia, an even more rare genetic disorder of neuromuscular transmission. “Congenital myasthenias will not improve with immune therapy, and patients will suffer complications for no reason,” he said. “A patient who is seronegative should be assessed for congenital myasthenia with the right clinical presentation. The condition would be more likely in patients with a family history of symptoms similar to MG. It may be symptomatic at birth, but patients may present in adulthood.”

Kaminski noted that his team is collecting saliva samples from patients with MuSK-MG, a rare MG subtype linked to more severe cases, for genetic testing and genome-wide association studies.

There was no study funding, and the authors have no disclosures. Kaminski is principal investigator of a rare disease network dedicated to MG.

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

SAVANNAH, GEORGIA — One patient with autoimmune myasthenia gravis (MG) has a niece with the same diagnosis, and at least one of his other close relatives may have it too. Another patient with MG lost his father and brother to complications from the disease, while a surviving brother also has it. These two cases, reported at a meeting of nerve/muscle specialists, spotlight one of the mysteries of MG: What role does heredity play in this disorder?

“Clinical familial associations — when transmission appears to be vertical, from parent to offspring — suggest that there is much yet to learn about genetic bases for autoimmunity and how certain mutations could favor selection for specific immune disorders,” said Elena Shanina, MD, PhD, a neurology professor at the University of Texas Medical Branch, Galveston, in an interview. She and colleagues presented the two case reports at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

As Shanina noted, MG is usually sporadic without a link to heredity. However, she said, research suggests that up to 7% of patients have MG in their family history.

“There are well-described genetic causes for congenital myasthenic syndromes, in which mutations occur in genes for neuromuscular junction (NMJ) proteins affecting NMJ function. However, much less is known about genetic associations to autoimmune MG,” she said.

“More than a decade ago, differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides were suggested to suffice in producing MG, and specific HLA DQ susceptibility links were found predisposing to MG. More recent studies have tried to identify specific genes such as CTLA4 mutations that enhance autoimmunity and neuroinflammation.”
 

Two Cases

In one of the case reports, a 75-year-old White man with hereditary coagulopathy presented with myasthenic crisis in the setting of acute pulmonary embolism. Chronic symptoms included diplopia, ptosis, and proximal muscle weakness.

A niece of the patient has been diagnosed with MG and suffers from ocular symptoms. Meanwhile, an uncle has ptosis but no diagnosis yet, and a daughter has dermatomyositis. Like MG, dermatomyositis is an autoimmune disease that causes muscle weakness.

The patient, who’s CTLA4 negative, is faring well on eculizumab after failing standard therapies, Shanina said.

In the other case, a 67-year-old Hispanic man presented with diplopia, generalized fatigue, and weakness. Like the other patient, he was seropositive for acetylcholine receptor antibodies.

This patient lost his father and brother to complications from MG. Another brother, who’s still living, also has MG.

“The patient has minimal manifestation status with disease and is currently controlled using oral immunomodulatory therapies,” Shanina said. “He is also CTLA4 negative.”
 

Genetics and Environment May Each Play a Role

Shanina called for research exploring mutations and inheritance patterns in families with MG.

“If there are genetic causes that increase autoimmunity with specific propensity for certain immune diseases, correcting those mutations could fundamentally change how we treat — and prevent — at least some autoimmune diseases,” she said. “For example, if HLA linkage is directly involved in determining susceptibility to MG, and if the presence of a specific HLA locus allele is sufficient to produce disease, HLA gene editing could be a future therapy to prevent such diseases. Likewise, monoclonal antibodies that target products of genes that increase risk for autoimmunity might be able to reduce such risks without modifying the patient’s genome.”

Henry J. Kaminski, MD, professor of neurology at George Washington University, Washington, DC, is familiar with the report’s findings. In an interview, he noted that while genetic profiles can make MG more likely, “the situation is not like Huntington’s or Alzheimer’s where there is a strong genetic risk.” 

Instead, he said, there’s “a genetic risk coupled to some environmental stimulus that leads to the development of MG, which is true for many complex autoimmune conditions.” 

While he doesn’t think the two new case reports are especially noteworthy, Kaminski said “the ability to assess genetic risk factors across patients will elucidate understanding of MG. Personalized medicine choices will likely require understanding of genetic risks.”

While understanding MG in families is “always good to know from a research perspective,” there’s no reason to launch surveillance of relatives to see if they also have the disease, he said.

Also, Kaminski cautioned that it’s important to differentiate autoimmune MG from congenital myasthenia, an even more rare genetic disorder of neuromuscular transmission. “Congenital myasthenias will not improve with immune therapy, and patients will suffer complications for no reason,” he said. “A patient who is seronegative should be assessed for congenital myasthenia with the right clinical presentation. The condition would be more likely in patients with a family history of symptoms similar to MG. It may be symptomatic at birth, but patients may present in adulthood.”

Kaminski noted that his team is collecting saliva samples from patients with MuSK-MG, a rare MG subtype linked to more severe cases, for genetic testing and genome-wide association studies.

There was no study funding, and the authors have no disclosures. Kaminski is principal investigator of a rare disease network dedicated to MG.

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

SAVANNAH, GEORGIA — One patient with autoimmune myasthenia gravis (MG) has a niece with the same diagnosis, and at least one of his other close relatives may have it too. Another patient with MG lost his father and brother to complications from the disease, while a surviving brother also has it. These two cases, reported at a meeting of nerve/muscle specialists, spotlight one of the mysteries of MG: What role does heredity play in this disorder?

“Clinical familial associations — when transmission appears to be vertical, from parent to offspring — suggest that there is much yet to learn about genetic bases for autoimmunity and how certain mutations could favor selection for specific immune disorders,” said Elena Shanina, MD, PhD, a neurology professor at the University of Texas Medical Branch, Galveston, in an interview. She and colleagues presented the two case reports at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

As Shanina noted, MG is usually sporadic without a link to heredity. However, she said, research suggests that up to 7% of patients have MG in their family history.

“There are well-described genetic causes for congenital myasthenic syndromes, in which mutations occur in genes for neuromuscular junction (NMJ) proteins affecting NMJ function. However, much less is known about genetic associations to autoimmune MG,” she said.

“More than a decade ago, differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides were suggested to suffice in producing MG, and specific HLA DQ susceptibility links were found predisposing to MG. More recent studies have tried to identify specific genes such as CTLA4 mutations that enhance autoimmunity and neuroinflammation.”
 

Two Cases

In one of the case reports, a 75-year-old White man with hereditary coagulopathy presented with myasthenic crisis in the setting of acute pulmonary embolism. Chronic symptoms included diplopia, ptosis, and proximal muscle weakness.

A niece of the patient has been diagnosed with MG and suffers from ocular symptoms. Meanwhile, an uncle has ptosis but no diagnosis yet, and a daughter has dermatomyositis. Like MG, dermatomyositis is an autoimmune disease that causes muscle weakness.

The patient, who’s CTLA4 negative, is faring well on eculizumab after failing standard therapies, Shanina said.

In the other case, a 67-year-old Hispanic man presented with diplopia, generalized fatigue, and weakness. Like the other patient, he was seropositive for acetylcholine receptor antibodies.

This patient lost his father and brother to complications from MG. Another brother, who’s still living, also has MG.

“The patient has minimal manifestation status with disease and is currently controlled using oral immunomodulatory therapies,” Shanina said. “He is also CTLA4 negative.”
 

Genetics and Environment May Each Play a Role

Shanina called for research exploring mutations and inheritance patterns in families with MG.

“If there are genetic causes that increase autoimmunity with specific propensity for certain immune diseases, correcting those mutations could fundamentally change how we treat — and prevent — at least some autoimmune diseases,” she said. “For example, if HLA linkage is directly involved in determining susceptibility to MG, and if the presence of a specific HLA locus allele is sufficient to produce disease, HLA gene editing could be a future therapy to prevent such diseases. Likewise, monoclonal antibodies that target products of genes that increase risk for autoimmunity might be able to reduce such risks without modifying the patient’s genome.”

Henry J. Kaminski, MD, professor of neurology at George Washington University, Washington, DC, is familiar with the report’s findings. In an interview, he noted that while genetic profiles can make MG more likely, “the situation is not like Huntington’s or Alzheimer’s where there is a strong genetic risk.” 

Instead, he said, there’s “a genetic risk coupled to some environmental stimulus that leads to the development of MG, which is true for many complex autoimmune conditions.” 

While he doesn’t think the two new case reports are especially noteworthy, Kaminski said “the ability to assess genetic risk factors across patients will elucidate understanding of MG. Personalized medicine choices will likely require understanding of genetic risks.”

While understanding MG in families is “always good to know from a research perspective,” there’s no reason to launch surveillance of relatives to see if they also have the disease, he said.

Also, Kaminski cautioned that it’s important to differentiate autoimmune MG from congenital myasthenia, an even more rare genetic disorder of neuromuscular transmission. “Congenital myasthenias will not improve with immune therapy, and patients will suffer complications for no reason,” he said. “A patient who is seronegative should be assessed for congenital myasthenia with the right clinical presentation. The condition would be more likely in patients with a family history of symptoms similar to MG. It may be symptomatic at birth, but patients may present in adulthood.”

Kaminski noted that his team is collecting saliva samples from patients with MuSK-MG, a rare MG subtype linked to more severe cases, for genetic testing and genome-wide association studies.

There was no study funding, and the authors have no disclosures. Kaminski is principal investigator of a rare disease network dedicated to MG.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

In a stunning verdict against Blue Cross and Blue Shield of Louisiana, a New Orleans jury has awarded $421 million in damages to a surgery center over the insurer’s alleged failure to fully pay out-of-network charges.

Insurance specialists told this news organization that the September 20 verdict is unusual. If upheld on appeal, one said, it could give out-of-network providers more power to decide how much insurers must pay them.

The case, which the St. Charles Surgical Hospital and Center for Restorative Breast Surgery first filed in 2017 in Louisiana state court, will be appealed and could ultimately land in federal court. The center has seen mixed results from a similar case it filed in federal court, legal documents show. Physicians from the center declined comment.

At issue: Did Blue Cross fail to fully pay the surgery center for about 7000 out-of-network procedures that it authorized? 

The lawsuit claimed that the insurer’s online system confirmed that claims would be paid and noted the percentage of patient bills that would be reimbursed.

However, “Blue Cross and Blue Shield of Louisiana either slow-paid, low-paid, or no-paid all their bills over an eight-year period, hoping to pressure the doctors and hospital to either come into the network or fail and close down,” the surgery center’s attorney, James Williams, said in a statement.

Blue Cross denied that it acted fraudulently, “arguing that because the hospital is not a member of its provider network, it had no contractual obligation to pay anything,” the Times-Picayune newspaper reported. Authorization of a procedure doesn’t guarantee payment, the insurer argued in court.

In a statement to the media, Blue Cross said it disagrees with the verdict and will appeal.
 

Out-of-Network Free For All

Paul B. Ginsburg, PhD, professor of the Practice of Health Policy at the Price School of Public Policy, University of Southern California, Los Angeles, said out-of-network care doesn’t come with a contractual relationship.

Without a contract, he said, “providers can charge whatever they want, and the insurers will pay them whatever they want, and then it’s up to the provider to see how much additional balance bill they can collect from the patients.” (Some states and the federal government have laws partly protecting patients from balance billing when doctors and insurers conflict over payment.)

He added that “if insurance companies were on the hook to pay whatever any provider charges, nobody would ever belong to a network, and rates would be sky high. Many fewer people would buy insurance. Providers would [then] charge as much as they think they can get from the patients.”

What about the insurer’s apparent authorization of the out-of-network procedures? “They’re authorizing them because they believe the procedures are medically warranted,” Dr. Ginsburg said. “That’s totally separate from how much they’ll pay.”

Dr. Ginsburg added that juries in the South are known for imposing high penalties against companies. “They often come up with crazy verdicts.”

Mark V. Pauly, PhD, MA, professor emeritus of health care management at the Wharton School of the University of Pennsylvania, Philadelphia, questioned why the clinic kept accepting Blue Cross patients.

“Once it became apparent that Blue Cross wasn’t going to pay them well or would give them a lot of grief,” Dr. Pauly said, “the simplest thing would have been to tell patients that we’re going to go back to the old-fashioned way of doing things: You pay us up front, or assure us that you’re going to pay.”

Lawton Robert Burns, PhD, MBA, professor of health care management at the Wharton School, said the case and the verdict are unusual. He noted that insurer contracts with employers often state that out-of-network care will be covered at a specific rate, such as 70% of “reasonable charges.”

A 2020 analysis found that initial breast reconstruction surgeries in the United States cost a median of $24,600-$38,000 from 2009 to 2016. According to the Times-Picayune, the New Orleans clinic billed Blue Cross for $506.7 million, averaging more than $72,385 per procedure.

Dr. Ginsburg, Dr. Pauly, and Dr. Burns had no disclosures.

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

In a stunning verdict against Blue Cross and Blue Shield of Louisiana, a New Orleans jury has awarded $421 million in damages to a surgery center over the insurer’s alleged failure to fully pay out-of-network charges.

Insurance specialists told this news organization that the September 20 verdict is unusual. If upheld on appeal, one said, it could give out-of-network providers more power to decide how much insurers must pay them.

The case, which the St. Charles Surgical Hospital and Center for Restorative Breast Surgery first filed in 2017 in Louisiana state court, will be appealed and could ultimately land in federal court. The center has seen mixed results from a similar case it filed in federal court, legal documents show. Physicians from the center declined comment.

At issue: Did Blue Cross fail to fully pay the surgery center for about 7000 out-of-network procedures that it authorized? 

The lawsuit claimed that the insurer’s online system confirmed that claims would be paid and noted the percentage of patient bills that would be reimbursed.

However, “Blue Cross and Blue Shield of Louisiana either slow-paid, low-paid, or no-paid all their bills over an eight-year period, hoping to pressure the doctors and hospital to either come into the network or fail and close down,” the surgery center’s attorney, James Williams, said in a statement.

Blue Cross denied that it acted fraudulently, “arguing that because the hospital is not a member of its provider network, it had no contractual obligation to pay anything,” the Times-Picayune newspaper reported. Authorization of a procedure doesn’t guarantee payment, the insurer argued in court.

In a statement to the media, Blue Cross said it disagrees with the verdict and will appeal.
 

Out-of-Network Free For All

Paul B. Ginsburg, PhD, professor of the Practice of Health Policy at the Price School of Public Policy, University of Southern California, Los Angeles, said out-of-network care doesn’t come with a contractual relationship.

Without a contract, he said, “providers can charge whatever they want, and the insurers will pay them whatever they want, and then it’s up to the provider to see how much additional balance bill they can collect from the patients.” (Some states and the federal government have laws partly protecting patients from balance billing when doctors and insurers conflict over payment.)

He added that “if insurance companies were on the hook to pay whatever any provider charges, nobody would ever belong to a network, and rates would be sky high. Many fewer people would buy insurance. Providers would [then] charge as much as they think they can get from the patients.”

What about the insurer’s apparent authorization of the out-of-network procedures? “They’re authorizing them because they believe the procedures are medically warranted,” Dr. Ginsburg said. “That’s totally separate from how much they’ll pay.”

Dr. Ginsburg added that juries in the South are known for imposing high penalties against companies. “They often come up with crazy verdicts.”

Mark V. Pauly, PhD, MA, professor emeritus of health care management at the Wharton School of the University of Pennsylvania, Philadelphia, questioned why the clinic kept accepting Blue Cross patients.

“Once it became apparent that Blue Cross wasn’t going to pay them well or would give them a lot of grief,” Dr. Pauly said, “the simplest thing would have been to tell patients that we’re going to go back to the old-fashioned way of doing things: You pay us up front, or assure us that you’re going to pay.”

Lawton Robert Burns, PhD, MBA, professor of health care management at the Wharton School, said the case and the verdict are unusual. He noted that insurer contracts with employers often state that out-of-network care will be covered at a specific rate, such as 70% of “reasonable charges.”

A 2020 analysis found that initial breast reconstruction surgeries in the United States cost a median of $24,600-$38,000 from 2009 to 2016. According to the Times-Picayune, the New Orleans clinic billed Blue Cross for $506.7 million, averaging more than $72,385 per procedure.

Dr. Ginsburg, Dr. Pauly, and Dr. Burns had no disclosures.

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

In a stunning verdict against Blue Cross and Blue Shield of Louisiana, a New Orleans jury has awarded $421 million in damages to a surgery center over the insurer’s alleged failure to fully pay out-of-network charges.

Insurance specialists told this news organization that the September 20 verdict is unusual. If upheld on appeal, one said, it could give out-of-network providers more power to decide how much insurers must pay them.

The case, which the St. Charles Surgical Hospital and Center for Restorative Breast Surgery first filed in 2017 in Louisiana state court, will be appealed and could ultimately land in federal court. The center has seen mixed results from a similar case it filed in federal court, legal documents show. Physicians from the center declined comment.

At issue: Did Blue Cross fail to fully pay the surgery center for about 7000 out-of-network procedures that it authorized? 

The lawsuit claimed that the insurer’s online system confirmed that claims would be paid and noted the percentage of patient bills that would be reimbursed.

However, “Blue Cross and Blue Shield of Louisiana either slow-paid, low-paid, or no-paid all their bills over an eight-year period, hoping to pressure the doctors and hospital to either come into the network or fail and close down,” the surgery center’s attorney, James Williams, said in a statement.

Blue Cross denied that it acted fraudulently, “arguing that because the hospital is not a member of its provider network, it had no contractual obligation to pay anything,” the Times-Picayune newspaper reported. Authorization of a procedure doesn’t guarantee payment, the insurer argued in court.

In a statement to the media, Blue Cross said it disagrees with the verdict and will appeal.
 

Out-of-Network Free For All

Paul B. Ginsburg, PhD, professor of the Practice of Health Policy at the Price School of Public Policy, University of Southern California, Los Angeles, said out-of-network care doesn’t come with a contractual relationship.

Without a contract, he said, “providers can charge whatever they want, and the insurers will pay them whatever they want, and then it’s up to the provider to see how much additional balance bill they can collect from the patients.” (Some states and the federal government have laws partly protecting patients from balance billing when doctors and insurers conflict over payment.)

He added that “if insurance companies were on the hook to pay whatever any provider charges, nobody would ever belong to a network, and rates would be sky high. Many fewer people would buy insurance. Providers would [then] charge as much as they think they can get from the patients.”

What about the insurer’s apparent authorization of the out-of-network procedures? “They’re authorizing them because they believe the procedures are medically warranted,” Dr. Ginsburg said. “That’s totally separate from how much they’ll pay.”

Dr. Ginsburg added that juries in the South are known for imposing high penalties against companies. “They often come up with crazy verdicts.”

Mark V. Pauly, PhD, MA, professor emeritus of health care management at the Wharton School of the University of Pennsylvania, Philadelphia, questioned why the clinic kept accepting Blue Cross patients.

“Once it became apparent that Blue Cross wasn’t going to pay them well or would give them a lot of grief,” Dr. Pauly said, “the simplest thing would have been to tell patients that we’re going to go back to the old-fashioned way of doing things: You pay us up front, or assure us that you’re going to pay.”

Lawton Robert Burns, PhD, MBA, professor of health care management at the Wharton School, said the case and the verdict are unusual. He noted that insurer contracts with employers often state that out-of-network care will be covered at a specific rate, such as 70% of “reasonable charges.”

A 2020 analysis found that initial breast reconstruction surgeries in the United States cost a median of $24,600-$38,000 from 2009 to 2016. According to the Times-Picayune, the New Orleans clinic billed Blue Cross for $506.7 million, averaging more than $72,385 per procedure.

Dr. Ginsburg, Dr. Pauly, and Dr. Burns 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.

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.

The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.

The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.

Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”

The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.

For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.

Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.

Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.

In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine. 

Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.

Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.

The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.

A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.

The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”

Bates reported that she had no disclosures.

The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.

The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.

Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”

The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.

For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.

Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.

Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.

In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine. 

Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.

Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.

The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.

A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.

The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”

Bates reported that she had no disclosures.

The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.

The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.

Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”

The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.

For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.

Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.

Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.

In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine. 

Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.

Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.

The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.

A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.

The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”

Bates reported that she had no disclosures.

Research conducted at the US Department of Veterans Affairs (VA) could offer crucial insight into the hotly debated question of whether patients with head and neck cancer should have access to percutaneous endoscopic gastrostomy (PEG) before they develop malnutrition.

While no definitive conclusions can be drawn until a complete study is performed, early findings of a pilot trial are intriguing, said advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, who spoke in an interview with Federal Practitioner and at the annual meeting of the Association of VA Hematology/Oncology.

So far, the 12 patients with head and neck cancer who agreed to the placement of prophylactic feeding tubes prior to chemoradiation have had worse outcomes in some areas compared to the 9 patients who had tubes inserted when clinically indicated and the 12 who didn't need feeding tubes.

Petersen cautioned that the study is small and underpowered at this point. Still, she noted, "We're seeing a hint of exactly the opposite of what I expected. Those who get a tube prophylactically are doing worse than those who are getting it reactively or not at all, If that's the case, that's a really important outcome."

As Petersen explained, the placement of PEG feeding tubes is a hot topic in head and neck cancer care. Malnutrition affects about 80% of these patients and can contribute to mortality, raising the question of whether they should have access to feeding tubes placed prior to treatment in case enteral nutrition is needed.

In some patients with head and neck cancer, malnutrition may arise when tumors block food intake or prevent patients from swallowing. "But in my clinical experience, most often it's from the adverse effects of radiation and chemotherapy. Radiation creates burns inside their throat that make it hard to swallow. Or they have taste changes or really dry mouth," Petersen said.

"On top of these problems, chemotherapy can cause nausea and vomiting," she said. Placing feeding tube access may seem like a smart strategy to head off malnutrition as soon as it occurs. But, as Petersen noted, feeding tube use can lead to dependency as patients lose their ability to swallow. "There's a theory that if we give people feeding tubes, they'll go with the easier route of using a feeding tube and not keep swallowing. Then those swallowing muscles would weaken, and patients would end up permanently on a feeding tube."

In 2020, a retrospective VA study linked feeding tube dependence to lower overall survival in head and neck cancer patients. There are also risks to feeding tube placement, such as infection, pain, leakage, and inflammation.

But what if feeding tube valves are inserted prophylactically so they can be used for nutrition if needed? "We just haven't had any prospective studies to get to the heart of the matter and answer the question," she said. "It's hard to recruit. How do you convince somebody to randomly be assigned to have a hole poked in their stomach?"

For the new pilot study, researchers in Phoenix decided not to randomize patients. Instead, they asked them whether they'd accept the placement of feeding tube valves on a prophylactic basis.

Thirty-six veterans enrolled in 3 years, 33% of those were eligible. Twelve have died, 1 withdrew, and 2 were lost to follow-up.

Those in the prophylactic group had worse physical function and muscle strength over time, while those who received feeding tubes when needed had more adverse events.

Why might some outcomes be worse for patients who chose the prophylactic approach? "The answer is unclear," Petersen said. "Although one possibility is that those patients had higher-risk tumors and were more clued into their own risk."

"The goal now is to get funding for an expanded, multicenter study within the VA," Petersen said. The big question that she hopes to answer is: Does a prophylactic approach work? "Does it make a difference for patients in terms of how quickly they go back to living a full, meaningful life and be able to do all the things that they normally would do?"

A complete study would likely last 7 years, but helpful results may come earlier. "We are starting to see significant differences in terms of our main outcomes of physical function," Petersen said. "We only need 1 to 2 years of data for each patient to get to the heart of that."

The study is not funded, and Petersen reported no disclosures.

Research conducted at the US Department of Veterans Affairs (VA) could offer crucial insight into the hotly debated question of whether patients with head and neck cancer should have access to percutaneous endoscopic gastrostomy (PEG) before they develop malnutrition.

While no definitive conclusions can be drawn until a complete study is performed, early findings of a pilot trial are intriguing, said advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, who spoke in an interview with Federal Practitioner and at the annual meeting of the Association of VA Hematology/Oncology.

So far, the 12 patients with head and neck cancer who agreed to the placement of prophylactic feeding tubes prior to chemoradiation have had worse outcomes in some areas compared to the 9 patients who had tubes inserted when clinically indicated and the 12 who didn't need feeding tubes.

Petersen cautioned that the study is small and underpowered at this point. Still, she noted, "We're seeing a hint of exactly the opposite of what I expected. Those who get a tube prophylactically are doing worse than those who are getting it reactively or not at all, If that's the case, that's a really important outcome."

As Petersen explained, the placement of PEG feeding tubes is a hot topic in head and neck cancer care. Malnutrition affects about 80% of these patients and can contribute to mortality, raising the question of whether they should have access to feeding tubes placed prior to treatment in case enteral nutrition is needed.

In some patients with head and neck cancer, malnutrition may arise when tumors block food intake or prevent patients from swallowing. "But in my clinical experience, most often it's from the adverse effects of radiation and chemotherapy. Radiation creates burns inside their throat that make it hard to swallow. Or they have taste changes or really dry mouth," Petersen said.

"On top of these problems, chemotherapy can cause nausea and vomiting," she said. Placing feeding tube access may seem like a smart strategy to head off malnutrition as soon as it occurs. But, as Petersen noted, feeding tube use can lead to dependency as patients lose their ability to swallow. "There's a theory that if we give people feeding tubes, they'll go with the easier route of using a feeding tube and not keep swallowing. Then those swallowing muscles would weaken, and patients would end up permanently on a feeding tube."

In 2020, a retrospective VA study linked feeding tube dependence to lower overall survival in head and neck cancer patients. There are also risks to feeding tube placement, such as infection, pain, leakage, and inflammation.

But what if feeding tube valves are inserted prophylactically so they can be used for nutrition if needed? "We just haven't had any prospective studies to get to the heart of the matter and answer the question," she said. "It's hard to recruit. How do you convince somebody to randomly be assigned to have a hole poked in their stomach?"

For the new pilot study, researchers in Phoenix decided not to randomize patients. Instead, they asked them whether they'd accept the placement of feeding tube valves on a prophylactic basis.

Thirty-six veterans enrolled in 3 years, 33% of those were eligible. Twelve have died, 1 withdrew, and 2 were lost to follow-up.

Those in the prophylactic group had worse physical function and muscle strength over time, while those who received feeding tubes when needed had more adverse events.

Why might some outcomes be worse for patients who chose the prophylactic approach? "The answer is unclear," Petersen said. "Although one possibility is that those patients had higher-risk tumors and were more clued into their own risk."

"The goal now is to get funding for an expanded, multicenter study within the VA," Petersen said. The big question that she hopes to answer is: Does a prophylactic approach work? "Does it make a difference for patients in terms of how quickly they go back to living a full, meaningful life and be able to do all the things that they normally would do?"

A complete study would likely last 7 years, but helpful results may come earlier. "We are starting to see significant differences in terms of our main outcomes of physical function," Petersen said. "We only need 1 to 2 years of data for each patient to get to the heart of that."

The study is not funded, and Petersen reported no disclosures.

Research conducted at the US Department of Veterans Affairs (VA) could offer crucial insight into the hotly debated question of whether patients with head and neck cancer should have access to percutaneous endoscopic gastrostomy (PEG) before they develop malnutrition.

While no definitive conclusions can be drawn until a complete study is performed, early findings of a pilot trial are intriguing, said advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, who spoke in an interview with Federal Practitioner and at the annual meeting of the Association of VA Hematology/Oncology.

So far, the 12 patients with head and neck cancer who agreed to the placement of prophylactic feeding tubes prior to chemoradiation have had worse outcomes in some areas compared to the 9 patients who had tubes inserted when clinically indicated and the 12 who didn't need feeding tubes.

Petersen cautioned that the study is small and underpowered at this point. Still, she noted, "We're seeing a hint of exactly the opposite of what I expected. Those who get a tube prophylactically are doing worse than those who are getting it reactively or not at all, If that's the case, that's a really important outcome."

As Petersen explained, the placement of PEG feeding tubes is a hot topic in head and neck cancer care. Malnutrition affects about 80% of these patients and can contribute to mortality, raising the question of whether they should have access to feeding tubes placed prior to treatment in case enteral nutrition is needed.

In some patients with head and neck cancer, malnutrition may arise when tumors block food intake or prevent patients from swallowing. "But in my clinical experience, most often it's from the adverse effects of radiation and chemotherapy. Radiation creates burns inside their throat that make it hard to swallow. Or they have taste changes or really dry mouth," Petersen said.

"On top of these problems, chemotherapy can cause nausea and vomiting," she said. Placing feeding tube access may seem like a smart strategy to head off malnutrition as soon as it occurs. But, as Petersen noted, feeding tube use can lead to dependency as patients lose their ability to swallow. "There's a theory that if we give people feeding tubes, they'll go with the easier route of using a feeding tube and not keep swallowing. Then those swallowing muscles would weaken, and patients would end up permanently on a feeding tube."

In 2020, a retrospective VA study linked feeding tube dependence to lower overall survival in head and neck cancer patients. There are also risks to feeding tube placement, such as infection, pain, leakage, and inflammation.

But what if feeding tube valves are inserted prophylactically so they can be used for nutrition if needed? "We just haven't had any prospective studies to get to the heart of the matter and answer the question," she said. "It's hard to recruit. How do you convince somebody to randomly be assigned to have a hole poked in their stomach?"

For the new pilot study, researchers in Phoenix decided not to randomize patients. Instead, they asked them whether they'd accept the placement of feeding tube valves on a prophylactic basis.

Thirty-six veterans enrolled in 3 years, 33% of those were eligible. Twelve have died, 1 withdrew, and 2 were lost to follow-up.

Those in the prophylactic group had worse physical function and muscle strength over time, while those who received feeding tubes when needed had more adverse events.

Why might some outcomes be worse for patients who chose the prophylactic approach? "The answer is unclear," Petersen said. "Although one possibility is that those patients had higher-risk tumors and were more clued into their own risk."

"The goal now is to get funding for an expanded, multicenter study within the VA," Petersen said. The big question that she hopes to answer is: Does a prophylactic approach work? "Does it make a difference for patients in terms of how quickly they go back to living a full, meaningful life and be able to do all the things that they normally would do?"

A complete study would likely last 7 years, but helpful results may come earlier. "We are starting to see significant differences in terms of our main outcomes of physical function," Petersen said. "We only need 1 to 2 years of data for each patient to get to the heart of that."

The study is not funded, and Petersen reported no disclosures.

Guinea pigs are important to Ohio State University leukemia specialist Kerry A. Rogers, MD, but not because they’re in her research laboratory, where the focus is on studying treatments for chronic lymphocytic leukemia (CLL), hairy cell leukemia, and autoimmune hemolytic anemia. Instead, two of these little creatures — Pancake and Maple — are pets who live with her at home. 

Sometimes, however, Dr. Rogers’ guinea pigs pay visits to her workplace. Every Halloween, she dresses them up and shows off their photos to just about everyone. Patients, coworkers, and even random people in the elevator get glimpses of the furry pair, who pose as dinosaurs, bats, aquarium shrimp, sharks, spiders, and bumblebees.

courtesy Ohio State University

“Being in the hospital is not funny, but guinea pigs dressed up for Halloween is incredibly funny,” Dr. Rogers said. “They make a lot of people smile.”

For physician-scientist Dr. Rogers, a native of suburban Chicago, quality of life for patients is a priority, even when she’s not trying to entertain them and lift their spirits.

The field of hematology “is trying to figure out not only what’s biologically effective for disease, but also what might be best for people living with the condition,” she said. “This is especially true in terms of patient preference for a treatment you complete vs an ongoing or continuous treatment. I really like this idea of having more attention paid to what matters to patients, which the field of medicine sometimes forgets.”

In an interview, Dr. Rogers spoke about the appeal of storytelling in medicine, advances in treatment for CLL and hairy cell leukemia, and the challenges of college football loyalty. 

How did you get drawn to medicine?

Ever since I was a kid, I thought, “Oh, I really want to be a doctor. That sounds fun.” At its core, medicine blends things I really like: science, helping people with a problem, and storytelling. 

The practice of medicine is a lot about stories — talking to people, figuring out what they’re telling you about what’s going on, then explaining what you know in a way that makes sense to them. 

What changes have you seen in leukemia care during your career?

The biggest change is the move from chemotherapies to targeted agents. When I first did a fellowship here at Ohio State, we had studies of ibrutinib, the first-in-class covalent Bruton tyrosine kinase (BTK) inhibitor. We’d see patients who’d been on chemotherapy for the past 10 or 15 years, and then they got in a clinical trial. Ibrutinib worked better than any of the chemotherapy, and they felt better and had fewer side effects. 

Now, chemoimmunotherapy is not recommended for CLL, and you can see the impact of targeted agents on the lives of patients. Instead of telling people they need to put aside work and personal plans to take intensive chemotherapy for 6 months, you say: “You’ve got to come to some more appointments to make sure the treatment is going well, and you don’t have too many side effects. But you can expect to continue to work full-time and go to your niece’s wedding out of state or whatever else you want to do.”

What are you most excited about working on? 

I’m the principal investigator of a study combining obinutuzumab, ibrutinib, and venetoclax for a fixed duration, a defined treatment course of a little over a year. I just reported the median progression-free survival for phase 2 at the European Hematology Association meeting this spring. It was over 7 years for both patients who had prior treatment and those who hadn’t. 

The idea that people could take a year of treatment and get a huge benefit after completing it is quite important. The regimen has gone into phase 3 testing, and we’re now trying to understand the impact in terms of which patients got longer responses or which didn’t. 

What are some challenges that remain in CLL?

There are still patients whose CLL becomes resistant to our two most commonly used classes of agents: BTK inhibitors and the BLC2 inhibitor, venetoclax. There are some more BCL2 inhibitors in development, but venetoclax is the only one currently approved.

I am also principal investigator on another study that added venetoclax to ibrutinib when resistance mutations developed that would predict ultimate resistance to ibrutinib. The median progression-free survival in that study was 40.7 months, whereas the expectation with venetoclax alone is 24 months. So, it really improved the amount of time people were in remission. This study is ongoing. 

We’ve just started a phase 2 study to have patients take pirtobrutinib, a noncovalent BTK inhibitor, in combination with venetoclax in cases where CLL has become resistant to a covalent BTK inhibitor. Patients will take this combination for about a year and a half. 

It’s been really exciting to see the impact of some of these combinations both as first-line CLL treatment and in CLL that’s become resistant. But trying to understand what predicts response is a harder thing. I wish I knew the answers for what causes this synergy between those two classes of drugs. 

You also specialize in hairy cell leukemia. Could you talk about what it is? 

CLL is the most prevalent adult leukemia in the Western world, whereas hairy cell leukemia is very rare. It’s a slow-growing B-cell cancer that got its name because under the microscope, the cells have hairy projections on them.

It had a survival of only about 2-4 years before the development of purine analogs. After a course of pentostatin or cladribine (2-chlordeoxyadenosine), some people never need treatment again in our natural lifespan. 

But some patients don’t benefit from purine analogs, either because they have a devastating infection that makes them unsuitable or for another reason. Or they end up needing treatment every 2-3 years, which isn’t something you want to do for 30 years of someone’s lifespan. 

What are some challenges in hairy cell leukemia?

It’s a rare condition, so it can be hard to do a really large clinical trial. A lot of physicians think that the prognosis is good and miss out on an opportunity for better treatment and to generate new knowledge.

Also, some people perceive that it’s not actually a problem for people living with it. Cladribine and pentostatin are not terrible chemotherapies, and most people tolerate them very well. But we can make treatment for hairy cell more effective and more tolerable for our patients if we put more effort into researching it. 

I’ve heard that you’re a big college football fan. How do you balance your history as a University of Michigan medical school alum with your work for archrival Ohio State? 

I went to Northwestern for undergrad, as did several people in my family. So, I usually just claim Northwestern is my football affiliation. It doesn’t inspire much vitriol if you cheer for Northwestern! 

And I understand that you live with a pair of guinea pigs. Do tell.

I adopted guinea pigs as pets in medical school. They’re cute and friendly, and they make all this noise for you when you come home. 

Courtesy Dr. Rogers

Once, one of my clinic patients said, “I don’t want to be your guinea pig.” I thought, “you should be so lucky.” They have quite a lifestyle: They’ve trained me to bring them vegetables, they nap most of the time, and they have a play space, a guinea pig playground. 

I thought I liked the guinea pigs more than they liked me. But last fall, I was gone for about 10 days. When I got back, I’d never heard them make so much noise. They were extremely happy to see me. Then for the next 48 hours, one would randomly start whistling for me to come over. I thought, “oh, these things do like me a little bit.”

Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Novartis, and AstraZeneca and consulting/advisory relationships with AstraZeneca, AbbVie, Genentech, Janssen, Pharmacyclics, BeiGene, Loxo@Lilly, and Alpine Immune Sciences. 

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

Guinea pigs are important to Ohio State University leukemia specialist Kerry A. Rogers, MD, but not because they’re in her research laboratory, where the focus is on studying treatments for chronic lymphocytic leukemia (CLL), hairy cell leukemia, and autoimmune hemolytic anemia. Instead, two of these little creatures — Pancake and Maple — are pets who live with her at home. 

Sometimes, however, Dr. Rogers’ guinea pigs pay visits to her workplace. Every Halloween, she dresses them up and shows off their photos to just about everyone. Patients, coworkers, and even random people in the elevator get glimpses of the furry pair, who pose as dinosaurs, bats, aquarium shrimp, sharks, spiders, and bumblebees.

courtesy Ohio State University

“Being in the hospital is not funny, but guinea pigs dressed up for Halloween is incredibly funny,” Dr. Rogers said. “They make a lot of people smile.”

For physician-scientist Dr. Rogers, a native of suburban Chicago, quality of life for patients is a priority, even when she’s not trying to entertain them and lift their spirits.

The field of hematology “is trying to figure out not only what’s biologically effective for disease, but also what might be best for people living with the condition,” she said. “This is especially true in terms of patient preference for a treatment you complete vs an ongoing or continuous treatment. I really like this idea of having more attention paid to what matters to patients, which the field of medicine sometimes forgets.”

In an interview, Dr. Rogers spoke about the appeal of storytelling in medicine, advances in treatment for CLL and hairy cell leukemia, and the challenges of college football loyalty. 

How did you get drawn to medicine?

Ever since I was a kid, I thought, “Oh, I really want to be a doctor. That sounds fun.” At its core, medicine blends things I really like: science, helping people with a problem, and storytelling. 

The practice of medicine is a lot about stories — talking to people, figuring out what they’re telling you about what’s going on, then explaining what you know in a way that makes sense to them. 

What changes have you seen in leukemia care during your career?

The biggest change is the move from chemotherapies to targeted agents. When I first did a fellowship here at Ohio State, we had studies of ibrutinib, the first-in-class covalent Bruton tyrosine kinase (BTK) inhibitor. We’d see patients who’d been on chemotherapy for the past 10 or 15 years, and then they got in a clinical trial. Ibrutinib worked better than any of the chemotherapy, and they felt better and had fewer side effects. 

Now, chemoimmunotherapy is not recommended for CLL, and you can see the impact of targeted agents on the lives of patients. Instead of telling people they need to put aside work and personal plans to take intensive chemotherapy for 6 months, you say: “You’ve got to come to some more appointments to make sure the treatment is going well, and you don’t have too many side effects. But you can expect to continue to work full-time and go to your niece’s wedding out of state or whatever else you want to do.”

What are you most excited about working on? 

I’m the principal investigator of a study combining obinutuzumab, ibrutinib, and venetoclax for a fixed duration, a defined treatment course of a little over a year. I just reported the median progression-free survival for phase 2 at the European Hematology Association meeting this spring. It was over 7 years for both patients who had prior treatment and those who hadn’t. 

The idea that people could take a year of treatment and get a huge benefit after completing it is quite important. The regimen has gone into phase 3 testing, and we’re now trying to understand the impact in terms of which patients got longer responses or which didn’t. 

What are some challenges that remain in CLL?

There are still patients whose CLL becomes resistant to our two most commonly used classes of agents: BTK inhibitors and the BLC2 inhibitor, venetoclax. There are some more BCL2 inhibitors in development, but venetoclax is the only one currently approved.

I am also principal investigator on another study that added venetoclax to ibrutinib when resistance mutations developed that would predict ultimate resistance to ibrutinib. The median progression-free survival in that study was 40.7 months, whereas the expectation with venetoclax alone is 24 months. So, it really improved the amount of time people were in remission. This study is ongoing. 

We’ve just started a phase 2 study to have patients take pirtobrutinib, a noncovalent BTK inhibitor, in combination with venetoclax in cases where CLL has become resistant to a covalent BTK inhibitor. Patients will take this combination for about a year and a half. 

It’s been really exciting to see the impact of some of these combinations both as first-line CLL treatment and in CLL that’s become resistant. But trying to understand what predicts response is a harder thing. I wish I knew the answers for what causes this synergy between those two classes of drugs. 

You also specialize in hairy cell leukemia. Could you talk about what it is? 

CLL is the most prevalent adult leukemia in the Western world, whereas hairy cell leukemia is very rare. It’s a slow-growing B-cell cancer that got its name because under the microscope, the cells have hairy projections on them.

It had a survival of only about 2-4 years before the development of purine analogs. After a course of pentostatin or cladribine (2-chlordeoxyadenosine), some people never need treatment again in our natural lifespan. 

But some patients don’t benefit from purine analogs, either because they have a devastating infection that makes them unsuitable or for another reason. Or they end up needing treatment every 2-3 years, which isn’t something you want to do for 30 years of someone’s lifespan. 

What are some challenges in hairy cell leukemia?

It’s a rare condition, so it can be hard to do a really large clinical trial. A lot of physicians think that the prognosis is good and miss out on an opportunity for better treatment and to generate new knowledge.

Also, some people perceive that it’s not actually a problem for people living with it. Cladribine and pentostatin are not terrible chemotherapies, and most people tolerate them very well. But we can make treatment for hairy cell more effective and more tolerable for our patients if we put more effort into researching it. 

I’ve heard that you’re a big college football fan. How do you balance your history as a University of Michigan medical school alum with your work for archrival Ohio State? 

I went to Northwestern for undergrad, as did several people in my family. So, I usually just claim Northwestern is my football affiliation. It doesn’t inspire much vitriol if you cheer for Northwestern! 

And I understand that you live with a pair of guinea pigs. Do tell.

I adopted guinea pigs as pets in medical school. They’re cute and friendly, and they make all this noise for you when you come home. 

Courtesy Dr. Rogers

Once, one of my clinic patients said, “I don’t want to be your guinea pig.” I thought, “you should be so lucky.” They have quite a lifestyle: They’ve trained me to bring them vegetables, they nap most of the time, and they have a play space, a guinea pig playground. 

I thought I liked the guinea pigs more than they liked me. But last fall, I was gone for about 10 days. When I got back, I’d never heard them make so much noise. They were extremely happy to see me. Then for the next 48 hours, one would randomly start whistling for me to come over. I thought, “oh, these things do like me a little bit.”

Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Novartis, and AstraZeneca and consulting/advisory relationships with AstraZeneca, AbbVie, Genentech, Janssen, Pharmacyclics, BeiGene, Loxo@Lilly, and Alpine Immune Sciences. 

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

Guinea pigs are important to Ohio State University leukemia specialist Kerry A. Rogers, MD, but not because they’re in her research laboratory, where the focus is on studying treatments for chronic lymphocytic leukemia (CLL), hairy cell leukemia, and autoimmune hemolytic anemia. Instead, two of these little creatures — Pancake and Maple — are pets who live with her at home. 

Sometimes, however, Dr. Rogers’ guinea pigs pay visits to her workplace. Every Halloween, she dresses them up and shows off their photos to just about everyone. Patients, coworkers, and even random people in the elevator get glimpses of the furry pair, who pose as dinosaurs, bats, aquarium shrimp, sharks, spiders, and bumblebees.

courtesy Ohio State University

“Being in the hospital is not funny, but guinea pigs dressed up for Halloween is incredibly funny,” Dr. Rogers said. “They make a lot of people smile.”

For physician-scientist Dr. Rogers, a native of suburban Chicago, quality of life for patients is a priority, even when she’s not trying to entertain them and lift their spirits.

The field of hematology “is trying to figure out not only what’s biologically effective for disease, but also what might be best for people living with the condition,” she said. “This is especially true in terms of patient preference for a treatment you complete vs an ongoing or continuous treatment. I really like this idea of having more attention paid to what matters to patients, which the field of medicine sometimes forgets.”

In an interview, Dr. Rogers spoke about the appeal of storytelling in medicine, advances in treatment for CLL and hairy cell leukemia, and the challenges of college football loyalty. 

How did you get drawn to medicine?

Ever since I was a kid, I thought, “Oh, I really want to be a doctor. That sounds fun.” At its core, medicine blends things I really like: science, helping people with a problem, and storytelling. 

The practice of medicine is a lot about stories — talking to people, figuring out what they’re telling you about what’s going on, then explaining what you know in a way that makes sense to them. 

What changes have you seen in leukemia care during your career?

The biggest change is the move from chemotherapies to targeted agents. When I first did a fellowship here at Ohio State, we had studies of ibrutinib, the first-in-class covalent Bruton tyrosine kinase (BTK) inhibitor. We’d see patients who’d been on chemotherapy for the past 10 or 15 years, and then they got in a clinical trial. Ibrutinib worked better than any of the chemotherapy, and they felt better and had fewer side effects. 

Now, chemoimmunotherapy is not recommended for CLL, and you can see the impact of targeted agents on the lives of patients. Instead of telling people they need to put aside work and personal plans to take intensive chemotherapy for 6 months, you say: “You’ve got to come to some more appointments to make sure the treatment is going well, and you don’t have too many side effects. But you can expect to continue to work full-time and go to your niece’s wedding out of state or whatever else you want to do.”

What are you most excited about working on? 

I’m the principal investigator of a study combining obinutuzumab, ibrutinib, and venetoclax for a fixed duration, a defined treatment course of a little over a year. I just reported the median progression-free survival for phase 2 at the European Hematology Association meeting this spring. It was over 7 years for both patients who had prior treatment and those who hadn’t. 

The idea that people could take a year of treatment and get a huge benefit after completing it is quite important. The regimen has gone into phase 3 testing, and we’re now trying to understand the impact in terms of which patients got longer responses or which didn’t. 

What are some challenges that remain in CLL?

There are still patients whose CLL becomes resistant to our two most commonly used classes of agents: BTK inhibitors and the BLC2 inhibitor, venetoclax. There are some more BCL2 inhibitors in development, but venetoclax is the only one currently approved.

I am also principal investigator on another study that added venetoclax to ibrutinib when resistance mutations developed that would predict ultimate resistance to ibrutinib. The median progression-free survival in that study was 40.7 months, whereas the expectation with venetoclax alone is 24 months. So, it really improved the amount of time people were in remission. This study is ongoing. 

We’ve just started a phase 2 study to have patients take pirtobrutinib, a noncovalent BTK inhibitor, in combination with venetoclax in cases where CLL has become resistant to a covalent BTK inhibitor. Patients will take this combination for about a year and a half. 

It’s been really exciting to see the impact of some of these combinations both as first-line CLL treatment and in CLL that’s become resistant. But trying to understand what predicts response is a harder thing. I wish I knew the answers for what causes this synergy between those two classes of drugs. 

You also specialize in hairy cell leukemia. Could you talk about what it is? 

CLL is the most prevalent adult leukemia in the Western world, whereas hairy cell leukemia is very rare. It’s a slow-growing B-cell cancer that got its name because under the microscope, the cells have hairy projections on them.

It had a survival of only about 2-4 years before the development of purine analogs. After a course of pentostatin or cladribine (2-chlordeoxyadenosine), some people never need treatment again in our natural lifespan. 

But some patients don’t benefit from purine analogs, either because they have a devastating infection that makes them unsuitable or for another reason. Or they end up needing treatment every 2-3 years, which isn’t something you want to do for 30 years of someone’s lifespan. 

What are some challenges in hairy cell leukemia?

It’s a rare condition, so it can be hard to do a really large clinical trial. A lot of physicians think that the prognosis is good and miss out on an opportunity for better treatment and to generate new knowledge.

Also, some people perceive that it’s not actually a problem for people living with it. Cladribine and pentostatin are not terrible chemotherapies, and most people tolerate them very well. But we can make treatment for hairy cell more effective and more tolerable for our patients if we put more effort into researching it. 

I’ve heard that you’re a big college football fan. How do you balance your history as a University of Michigan medical school alum with your work for archrival Ohio State? 

I went to Northwestern for undergrad, as did several people in my family. So, I usually just claim Northwestern is my football affiliation. It doesn’t inspire much vitriol if you cheer for Northwestern! 

And I understand that you live with a pair of guinea pigs. Do tell.

I adopted guinea pigs as pets in medical school. They’re cute and friendly, and they make all this noise for you when you come home. 

Courtesy Dr. Rogers

Once, one of my clinic patients said, “I don’t want to be your guinea pig.” I thought, “you should be so lucky.” They have quite a lifestyle: They’ve trained me to bring them vegetables, they nap most of the time, and they have a play space, a guinea pig playground. 

I thought I liked the guinea pigs more than they liked me. But last fall, I was gone for about 10 days. When I got back, I’d never heard them make so much noise. They were extremely happy to see me. Then for the next 48 hours, one would randomly start whistling for me to come over. I thought, “oh, these things do like me a little bit.”

Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Novartis, and AstraZeneca and consulting/advisory relationships with AstraZeneca, AbbVie, Genentech, Janssen, Pharmacyclics, BeiGene, Loxo@Lilly, and Alpine Immune Sciences. 

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