Rare Diseases

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.

SAVANNAH, GEORGIA – The investigational monoclonal antibody nipocalimab (Johnson & Johnson) is associated with significant improvement in patients with generalized myasthenia gravis (gMG) over a 24-week period, according to topline results from the phase 3 VIVACITY-MG3 study.

The VIVACITY-MG3 trial is the first registrational study of a neonatal fragment crystallizable receptor (FcRn) blocker to show sustained efficacy through 6 months of fixed schedule dosing.

Lead investigator Tuan Vu, MD, professor of neurology at the University of South Florida in Tampa, presented the findings at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. 
 

Autoantibody Depletion

FcRN plays a crucial role in the transport of immunoglobulin G. Blocking it can reduce circulating immunoglobulin G antibodies, including pathogenic gMG autoantibodies. 

The double-blind, placebo-controlled trial included 196 adults with a broad range of seropositive gMG – who account for approximately 95% of the gMG patient population – and 42 seronegative patients.

The mean age was 52 years, 92% were female, and 63% were White. The mean disease duration was about 8 years. Among seropositive patients, 87.6% were acetylcholine receptor autoantibody-positive (AChR+), 10.5% were muscle-specific kinase autoantibody-positive (MuSK+), and 2% were low-density lipoprotein receptor-related protein 4 antibody positive.

They were randomly assigned 1:1 to receive either nipocalimab IV plus standard of care, or placebo plus standard of care for 24 weeks. A total of 87 patients in the nipocalimab arm and 82 in the placebo arm completed the study.

The primary efficacy endpoint was the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Participants treated with nipocalimab demonstrated a statistically significant improvement of 4.70 points from baseline, compared to the 3.25-point improvement in those treated with placebo (P =.002). 
 

Clinically Meaningful Changes?

“For someone living with gMG, a 1 to 2-point improvement on MG-ADL may be the difference between normal eating and frequent choking on food, or shortness of breath at rest and being on a ventilator,” the drug’s manufacturer noted in a release. 

Secondary endpoints were also better in the nipocalimab group, compared with participants on placebo. Specifically, on the 13-item clinician assessed Quantitative Myasthenia Gravis disease severity score, patients who received nipocalimab had an average reduction of 4.86 points from baseline compared to a reduction of 2.05 points in the placebo arm (P <.001). 

Similarly, MG-ADL response (defined as ≥ 2-point improvement from baseline) was significantly greater in the nipocalimab versus placebo arms (68.8% vs 52.6%; P =.021).

Subgroup analysis revealed similar results for the different types of seropositive patients, but there was no statistically significant difference in results for seronegative patients treated with nipocalimab versus placebo.

“The drug was pretty well tolerated and there was little difference, other than more patients with muscle spasm in the nipocalimab group (12.2% vs 3.1%),” said Vu. 

In addition, peripheral edema occurred in 11.2% of the nipocalimab group and none of the placebo-treated patients. Cholesterol levels were also higher in the nipocalimab arm, but there were no cardiac side effects, he added.
 

Encouraging Findings

Commenting on the findings, Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California, was encouraged.

“It’s a phase 3 trial, it’s positive, which is great, so it’ll be another drug on the market, another option for our patients,” she said. However, she cautioned, “their placebo arm did better than most placebos, so I think the delta is not as robust, but it was still statistically significant.” 

Goyal noted that, if approved, nipocalimab will be the third FcRn inhibitor in the MG field, preceded by efgartigimod (Vyvgart), which is approved for AChR antibody-positive disease, and rozanolixizumab-noli (Rystiggo) which is approved for both for AChR and MUSK antibody positive disease. 

“Its target of action is similar to the two drugs that are already on the market, but one thing that is unique about nipocalimab is that it is continuous dosing versus the other two medications that are given cyclically,” she said. 

“The reason that’s an upside, is that with cyclical dosing, patients have a return of symptoms. We treat, they get better, and then they get worse. That’s very disconcerting to patients. So, they want to be treated continuously.”

Additionally, she said there are some early data suggesting its safety in pregnancy.

Vu disclosed he is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion/ AstraZeneca Rare Disease, Amgen, argenx, Cartesian Therapeutics, COUR Pharmaceuticals, Dianthus Therapeutics, Immunovant, Johnson & Johnson, NMD Pharmaceuticals, Regeneron Pharmaceuticals, and UCB, and has served as a speaker for Alexion/AstraZeneca Rare Disease, argenx, and CSL Behring. He performs consulting work for Alexion/AstraZeneca Rare Disease, argenx, Dianthus Therapeutics, ImmunAbs, and UCB. Goyal disclosed consultant, advisory or grant support from argenx, UCB, Alexion, and Janssen. The study was funded by Janssen. 
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA – The investigational monoclonal antibody nipocalimab (Johnson & Johnson) is associated with significant improvement in patients with generalized myasthenia gravis (gMG) over a 24-week period, according to topline results from the phase 3 VIVACITY-MG3 study.

The VIVACITY-MG3 trial is the first registrational study of a neonatal fragment crystallizable receptor (FcRn) blocker to show sustained efficacy through 6 months of fixed schedule dosing.

Lead investigator Tuan Vu, MD, professor of neurology at the University of South Florida in Tampa, presented the findings at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. 
 

Autoantibody Depletion

FcRN plays a crucial role in the transport of immunoglobulin G. Blocking it can reduce circulating immunoglobulin G antibodies, including pathogenic gMG autoantibodies. 

The double-blind, placebo-controlled trial included 196 adults with a broad range of seropositive gMG – who account for approximately 95% of the gMG patient population – and 42 seronegative patients.

The mean age was 52 years, 92% were female, and 63% were White. The mean disease duration was about 8 years. Among seropositive patients, 87.6% were acetylcholine receptor autoantibody-positive (AChR+), 10.5% were muscle-specific kinase autoantibody-positive (MuSK+), and 2% were low-density lipoprotein receptor-related protein 4 antibody positive.

They were randomly assigned 1:1 to receive either nipocalimab IV plus standard of care, or placebo plus standard of care for 24 weeks. A total of 87 patients in the nipocalimab arm and 82 in the placebo arm completed the study.

The primary efficacy endpoint was the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Participants treated with nipocalimab demonstrated a statistically significant improvement of 4.70 points from baseline, compared to the 3.25-point improvement in those treated with placebo (P =.002). 
 

Clinically Meaningful Changes?

“For someone living with gMG, a 1 to 2-point improvement on MG-ADL may be the difference between normal eating and frequent choking on food, or shortness of breath at rest and being on a ventilator,” the drug’s manufacturer noted in a release. 

Secondary endpoints were also better in the nipocalimab group, compared with participants on placebo. Specifically, on the 13-item clinician assessed Quantitative Myasthenia Gravis disease severity score, patients who received nipocalimab had an average reduction of 4.86 points from baseline compared to a reduction of 2.05 points in the placebo arm (P <.001). 

Similarly, MG-ADL response (defined as ≥ 2-point improvement from baseline) was significantly greater in the nipocalimab versus placebo arms (68.8% vs 52.6%; P =.021).

Subgroup analysis revealed similar results for the different types of seropositive patients, but there was no statistically significant difference in results for seronegative patients treated with nipocalimab versus placebo.

“The drug was pretty well tolerated and there was little difference, other than more patients with muscle spasm in the nipocalimab group (12.2% vs 3.1%),” said Vu. 

In addition, peripheral edema occurred in 11.2% of the nipocalimab group and none of the placebo-treated patients. Cholesterol levels were also higher in the nipocalimab arm, but there were no cardiac side effects, he added.
 

Encouraging Findings

Commenting on the findings, Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California, was encouraged.

“It’s a phase 3 trial, it’s positive, which is great, so it’ll be another drug on the market, another option for our patients,” she said. However, she cautioned, “their placebo arm did better than most placebos, so I think the delta is not as robust, but it was still statistically significant.” 

Goyal noted that, if approved, nipocalimab will be the third FcRn inhibitor in the MG field, preceded by efgartigimod (Vyvgart), which is approved for AChR antibody-positive disease, and rozanolixizumab-noli (Rystiggo) which is approved for both for AChR and MUSK antibody positive disease. 

“Its target of action is similar to the two drugs that are already on the market, but one thing that is unique about nipocalimab is that it is continuous dosing versus the other two medications that are given cyclically,” she said. 

“The reason that’s an upside, is that with cyclical dosing, patients have a return of symptoms. We treat, they get better, and then they get worse. That’s very disconcerting to patients. So, they want to be treated continuously.”

Additionally, she said there are some early data suggesting its safety in pregnancy.

Vu disclosed he is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion/ AstraZeneca Rare Disease, Amgen, argenx, Cartesian Therapeutics, COUR Pharmaceuticals, Dianthus Therapeutics, Immunovant, Johnson & Johnson, NMD Pharmaceuticals, Regeneron Pharmaceuticals, and UCB, and has served as a speaker for Alexion/AstraZeneca Rare Disease, argenx, and CSL Behring. He performs consulting work for Alexion/AstraZeneca Rare Disease, argenx, Dianthus Therapeutics, ImmunAbs, and UCB. Goyal disclosed consultant, advisory or grant support from argenx, UCB, Alexion, and Janssen. The study was funded by Janssen. 
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA – The investigational monoclonal antibody nipocalimab (Johnson & Johnson) is associated with significant improvement in patients with generalized myasthenia gravis (gMG) over a 24-week period, according to topline results from the phase 3 VIVACITY-MG3 study.

The VIVACITY-MG3 trial is the first registrational study of a neonatal fragment crystallizable receptor (FcRn) blocker to show sustained efficacy through 6 months of fixed schedule dosing.

Lead investigator Tuan Vu, MD, professor of neurology at the University of South Florida in Tampa, presented the findings at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. 
 

Autoantibody Depletion

FcRN plays a crucial role in the transport of immunoglobulin G. Blocking it can reduce circulating immunoglobulin G antibodies, including pathogenic gMG autoantibodies. 

The double-blind, placebo-controlled trial included 196 adults with a broad range of seropositive gMG – who account for approximately 95% of the gMG patient population – and 42 seronegative patients.

The mean age was 52 years, 92% were female, and 63% were White. The mean disease duration was about 8 years. Among seropositive patients, 87.6% were acetylcholine receptor autoantibody-positive (AChR+), 10.5% were muscle-specific kinase autoantibody-positive (MuSK+), and 2% were low-density lipoprotein receptor-related protein 4 antibody positive.

They were randomly assigned 1:1 to receive either nipocalimab IV plus standard of care, or placebo plus standard of care for 24 weeks. A total of 87 patients in the nipocalimab arm and 82 in the placebo arm completed the study.

The primary efficacy endpoint was the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Participants treated with nipocalimab demonstrated a statistically significant improvement of 4.70 points from baseline, compared to the 3.25-point improvement in those treated with placebo (P =.002). 
 

Clinically Meaningful Changes?

“For someone living with gMG, a 1 to 2-point improvement on MG-ADL may be the difference between normal eating and frequent choking on food, or shortness of breath at rest and being on a ventilator,” the drug’s manufacturer noted in a release. 

Secondary endpoints were also better in the nipocalimab group, compared with participants on placebo. Specifically, on the 13-item clinician assessed Quantitative Myasthenia Gravis disease severity score, patients who received nipocalimab had an average reduction of 4.86 points from baseline compared to a reduction of 2.05 points in the placebo arm (P <.001). 

Similarly, MG-ADL response (defined as ≥ 2-point improvement from baseline) was significantly greater in the nipocalimab versus placebo arms (68.8% vs 52.6%; P =.021).

Subgroup analysis revealed similar results for the different types of seropositive patients, but there was no statistically significant difference in results for seronegative patients treated with nipocalimab versus placebo.

“The drug was pretty well tolerated and there was little difference, other than more patients with muscle spasm in the nipocalimab group (12.2% vs 3.1%),” said Vu. 

In addition, peripheral edema occurred in 11.2% of the nipocalimab group and none of the placebo-treated patients. Cholesterol levels were also higher in the nipocalimab arm, but there were no cardiac side effects, he added.
 

Encouraging Findings

Commenting on the findings, Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California, was encouraged.

“It’s a phase 3 trial, it’s positive, which is great, so it’ll be another drug on the market, another option for our patients,” she said. However, she cautioned, “their placebo arm did better than most placebos, so I think the delta is not as robust, but it was still statistically significant.” 

Goyal noted that, if approved, nipocalimab will be the third FcRn inhibitor in the MG field, preceded by efgartigimod (Vyvgart), which is approved for AChR antibody-positive disease, and rozanolixizumab-noli (Rystiggo) which is approved for both for AChR and MUSK antibody positive disease. 

“Its target of action is similar to the two drugs that are already on the market, but one thing that is unique about nipocalimab is that it is continuous dosing versus the other two medications that are given cyclically,” she said. 

“The reason that’s an upside, is that with cyclical dosing, patients have a return of symptoms. We treat, they get better, and then they get worse. That’s very disconcerting to patients. So, they want to be treated continuously.”

Additionally, she said there are some early data suggesting its safety in pregnancy.

Vu disclosed he is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion/ AstraZeneca Rare Disease, Amgen, argenx, Cartesian Therapeutics, COUR Pharmaceuticals, Dianthus Therapeutics, Immunovant, Johnson & Johnson, NMD Pharmaceuticals, Regeneron Pharmaceuticals, and UCB, and has served as a speaker for Alexion/AstraZeneca Rare Disease, argenx, and CSL Behring. He performs consulting work for Alexion/AstraZeneca Rare Disease, argenx, Dianthus Therapeutics, ImmunAbs, and UCB. Goyal disclosed consultant, advisory or grant support from argenx, UCB, Alexion, and Janssen. The study was funded by Janssen. 
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Inebilizumab, a first-in-class anti-CD19 B-cell depleting agent, demonstrated both safety and superior efficacy compared with placebo in patients with seropositive generalized myasthenia gravis (gMG), new phase 3 data showed.

“Based on these results, we have demonstrated that targeting B cells, including the antibody-secreting cells, is beneficial, and there is likely a role for this kind of therapeutic strategy for patients with myasthenia gravis,” said senior investigator Richard Nowak, MD.

The findings were published and presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Largest Cohort of Muscle-Specific Kinase (MuSK) Antibody–Positive Disease

The Myasthenia Gravis INebilizumab Trial study enrolled 238 participants, 60.8% women, mean age 47.5 years, from 79 sites in 18 countries. The participants were divided into two cohorts: 190 acetylcholine receptor (AChR) autoantibody–positive patients and 48 MuSK autoantibody–positive patients.

“This is the largest enrolled cohort of MuSK antibody–positive disease in a placebo-controlled trial to date,” said Nowak, director of the Yale Myasthenia Gravis Clinic and associate professor of neurology at Yale School of Medicine, in New Haven, Connecticut.

Both groups had similar gMG duration (mean 6.7 and 5.2 years for AChR+ and MuSK+ patients, respectively) and disease severity based on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) baseline score. In addition, more than 80% of participants were on a prednisone equivalent dose greater than 5 mg daily at study entry.

Participants were randomly assigned to receive intravenous (IV) inebilizumab or IV placebo for 52 weeks (AChR+ group) or 26 weeks (MuSK+ group). In addition, study participants who were taking corticosteroids were tapered down starting at week 4 to prednisone 5 mg per day by week 24.

The trial met its primary endpoint, with a statistically significant change from baseline in MG-ADL and with a reduction of 4.2 points for inebilizumab versus 2.2 for placebo (P < .0001) at week 26 for the combined study population.

“You can see that the trend is actually going toward separation of the two groups after week 8 in the combined population,” said Nowak. Key secondary endpoints also showed statistically significant and clinically meaningful change from baseline compared with placebo.

This included a statistically significant change in QMG score inebilizumab compared with placebo for the combined population, a reduction of 4.8 versus 2.3 points, respectively, at week 26 (P = .0002).

In addition, both MG-ADL and QMG scores in the AChR+ subgroup were superior for inebilizumab versus placebo at week 26, with reductions of 4.2 versus 2.4, and 4.4 versus 2.0; P = .0015 and P = .0011, respectively.

In the MuSK+ subgroup, inebilizumab-treated patients had better MG-ADL scores than placebo-treated patients, with reductions of 3.9 versus 1.7 points, respectively, at week 26, although this difference did not meet statistical significance.

“There were no increased safety incidents in the inebilizumab-treated patients versus placebo, and a similar percentage of safety incidents in the AChR–positive and MuSK–positive groups. There were three deaths reported, all likely related to myasthenic crisis,” he said.

Nowak said that inebilizumab is “unique from the other currently FDA-approved medications for myasthenia gravis in that it’s targeting the upstream immunopathogenic mechanism of disease, specifically B cells — and B cells that are actually antibody-secreting cells.”

“It is targeting the factories of autoantibody production, whereas an FcRn antagonist, for example, is not targeting those factories but rather targeting what’s being produced — the immunoglobulins, IgGs in general,” he added.

Nowak said that what is particularly exciting about the drug is that the schedule is not very frequent. It begins with an initial IV infusion, followed by a second infusion 2 weeks later and a third infusion 6 months after that, so that patients are treated approximately every 6 months. This is in contrast to some other targeted therapies, where failing to address the underlying factors driving immunopathogenesis necessitates more regular and frequent medication administration.
 

New, Novel, Exciting

Commenting on the research, Neelam Goyal, MD, who chaired the session, said, “It’s definitely new, novel, interesting, exciting.”

Goyal, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California, also noted that while B-cell depletion has shown some previous success in MG, it was with rituximab, a CD20 B-cell depleting agent.

She noted that unlike rituximab, which targets CD20, inebilizumab targets CD19, although both medications lead to B-cell depletion. Rituximab has proven effective for MUSK–positive MG, which accounts for approximately 5% of cases.

However, Goyal noted that the results for AChR–positive MG have been mixed — “the BeatMG trial was negative and the RINOMAX trial was positive. So, I think this is really interesting. It is exciting, and this drug is already on the market.”

She added that although inebilizumab is already US Food and Drug Administration–approved for the treatment of neuromyelitis optica, it still faces approval and indication hurdles for MG.

The future of this drug in the management algorithm for MG remains uncertain. Goyal noted that it’s “quite costly,” and although its benefits are evident — particularly for FcRn and complement inhibitors — some early data from chimeric antigen receptor T-cell therapy studies appear significantly more impressive.

Nowak disclosed research support from the National Institutes of Health, Genentech, Alexion Pharmaceuticals, argenx, Annexon Biosciences, Ra Pharmaceuticals (now UCB S.A.), the Myasthenia Gravis Foundation of America, Momenta Pharmaceuticals (now Janssen), Immunovant, Grifols, S.A., and Viela Bio, Horizon Therapeutics (now Amgen). Served as a consultant and advisor for Alexion Pharmaceuticals, argenx, Cabaletta Bio, Cour Pharmaceuticals, Ra Pharmaceuticals (now UCB S.A.), Immunovant, Momenta Pharmaceuticals (now Janssen), and Viela Bio (Horizon Therapeutics, now Amgen).

Goyal disclosed consultant, advisory, or grant support from argenx, UCB, Alexion, and Janssen. The study was funded by Amgen.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Inebilizumab, a first-in-class anti-CD19 B-cell depleting agent, demonstrated both safety and superior efficacy compared with placebo in patients with seropositive generalized myasthenia gravis (gMG), new phase 3 data showed.

“Based on these results, we have demonstrated that targeting B cells, including the antibody-secreting cells, is beneficial, and there is likely a role for this kind of therapeutic strategy for patients with myasthenia gravis,” said senior investigator Richard Nowak, MD.

The findings were published and presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Largest Cohort of Muscle-Specific Kinase (MuSK) Antibody–Positive Disease

The Myasthenia Gravis INebilizumab Trial study enrolled 238 participants, 60.8% women, mean age 47.5 years, from 79 sites in 18 countries. The participants were divided into two cohorts: 190 acetylcholine receptor (AChR) autoantibody–positive patients and 48 MuSK autoantibody–positive patients.

“This is the largest enrolled cohort of MuSK antibody–positive disease in a placebo-controlled trial to date,” said Nowak, director of the Yale Myasthenia Gravis Clinic and associate professor of neurology at Yale School of Medicine, in New Haven, Connecticut.

Both groups had similar gMG duration (mean 6.7 and 5.2 years for AChR+ and MuSK+ patients, respectively) and disease severity based on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) baseline score. In addition, more than 80% of participants were on a prednisone equivalent dose greater than 5 mg daily at study entry.

Participants were randomly assigned to receive intravenous (IV) inebilizumab or IV placebo for 52 weeks (AChR+ group) or 26 weeks (MuSK+ group). In addition, study participants who were taking corticosteroids were tapered down starting at week 4 to prednisone 5 mg per day by week 24.

The trial met its primary endpoint, with a statistically significant change from baseline in MG-ADL and with a reduction of 4.2 points for inebilizumab versus 2.2 for placebo (P < .0001) at week 26 for the combined study population.

“You can see that the trend is actually going toward separation of the two groups after week 8 in the combined population,” said Nowak. Key secondary endpoints also showed statistically significant and clinically meaningful change from baseline compared with placebo.

This included a statistically significant change in QMG score inebilizumab compared with placebo for the combined population, a reduction of 4.8 versus 2.3 points, respectively, at week 26 (P = .0002).

In addition, both MG-ADL and QMG scores in the AChR+ subgroup were superior for inebilizumab versus placebo at week 26, with reductions of 4.2 versus 2.4, and 4.4 versus 2.0; P = .0015 and P = .0011, respectively.

In the MuSK+ subgroup, inebilizumab-treated patients had better MG-ADL scores than placebo-treated patients, with reductions of 3.9 versus 1.7 points, respectively, at week 26, although this difference did not meet statistical significance.

“There were no increased safety incidents in the inebilizumab-treated patients versus placebo, and a similar percentage of safety incidents in the AChR–positive and MuSK–positive groups. There were three deaths reported, all likely related to myasthenic crisis,” he said.

Nowak said that inebilizumab is “unique from the other currently FDA-approved medications for myasthenia gravis in that it’s targeting the upstream immunopathogenic mechanism of disease, specifically B cells — and B cells that are actually antibody-secreting cells.”

“It is targeting the factories of autoantibody production, whereas an FcRn antagonist, for example, is not targeting those factories but rather targeting what’s being produced — the immunoglobulins, IgGs in general,” he added.

Nowak said that what is particularly exciting about the drug is that the schedule is not very frequent. It begins with an initial IV infusion, followed by a second infusion 2 weeks later and a third infusion 6 months after that, so that patients are treated approximately every 6 months. This is in contrast to some other targeted therapies, where failing to address the underlying factors driving immunopathogenesis necessitates more regular and frequent medication administration.
 

New, Novel, Exciting

Commenting on the research, Neelam Goyal, MD, who chaired the session, said, “It’s definitely new, novel, interesting, exciting.”

Goyal, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California, also noted that while B-cell depletion has shown some previous success in MG, it was with rituximab, a CD20 B-cell depleting agent.

She noted that unlike rituximab, which targets CD20, inebilizumab targets CD19, although both medications lead to B-cell depletion. Rituximab has proven effective for MUSK–positive MG, which accounts for approximately 5% of cases.

However, Goyal noted that the results for AChR–positive MG have been mixed — “the BeatMG trial was negative and the RINOMAX trial was positive. So, I think this is really interesting. It is exciting, and this drug is already on the market.”

She added that although inebilizumab is already US Food and Drug Administration–approved for the treatment of neuromyelitis optica, it still faces approval and indication hurdles for MG.

The future of this drug in the management algorithm for MG remains uncertain. Goyal noted that it’s “quite costly,” and although its benefits are evident — particularly for FcRn and complement inhibitors — some early data from chimeric antigen receptor T-cell therapy studies appear significantly more impressive.

Nowak disclosed research support from the National Institutes of Health, Genentech, Alexion Pharmaceuticals, argenx, Annexon Biosciences, Ra Pharmaceuticals (now UCB S.A.), the Myasthenia Gravis Foundation of America, Momenta Pharmaceuticals (now Janssen), Immunovant, Grifols, S.A., and Viela Bio, Horizon Therapeutics (now Amgen). Served as a consultant and advisor for Alexion Pharmaceuticals, argenx, Cabaletta Bio, Cour Pharmaceuticals, Ra Pharmaceuticals (now UCB S.A.), Immunovant, Momenta Pharmaceuticals (now Janssen), and Viela Bio (Horizon Therapeutics, now Amgen).

Goyal disclosed consultant, advisory, or grant support from argenx, UCB, Alexion, and Janssen. The study was funded by Amgen.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Inebilizumab, a first-in-class anti-CD19 B-cell depleting agent, demonstrated both safety and superior efficacy compared with placebo in patients with seropositive generalized myasthenia gravis (gMG), new phase 3 data showed.

“Based on these results, we have demonstrated that targeting B cells, including the antibody-secreting cells, is beneficial, and there is likely a role for this kind of therapeutic strategy for patients with myasthenia gravis,” said senior investigator Richard Nowak, MD.

The findings were published and presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Largest Cohort of Muscle-Specific Kinase (MuSK) Antibody–Positive Disease

The Myasthenia Gravis INebilizumab Trial study enrolled 238 participants, 60.8% women, mean age 47.5 years, from 79 sites in 18 countries. The participants were divided into two cohorts: 190 acetylcholine receptor (AChR) autoantibody–positive patients and 48 MuSK autoantibody–positive patients.

“This is the largest enrolled cohort of MuSK antibody–positive disease in a placebo-controlled trial to date,” said Nowak, director of the Yale Myasthenia Gravis Clinic and associate professor of neurology at Yale School of Medicine, in New Haven, Connecticut.

Both groups had similar gMG duration (mean 6.7 and 5.2 years for AChR+ and MuSK+ patients, respectively) and disease severity based on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) baseline score. In addition, more than 80% of participants were on a prednisone equivalent dose greater than 5 mg daily at study entry.

Participants were randomly assigned to receive intravenous (IV) inebilizumab or IV placebo for 52 weeks (AChR+ group) or 26 weeks (MuSK+ group). In addition, study participants who were taking corticosteroids were tapered down starting at week 4 to prednisone 5 mg per day by week 24.

The trial met its primary endpoint, with a statistically significant change from baseline in MG-ADL and with a reduction of 4.2 points for inebilizumab versus 2.2 for placebo (P < .0001) at week 26 for the combined study population.

“You can see that the trend is actually going toward separation of the two groups after week 8 in the combined population,” said Nowak. Key secondary endpoints also showed statistically significant and clinically meaningful change from baseline compared with placebo.

This included a statistically significant change in QMG score inebilizumab compared with placebo for the combined population, a reduction of 4.8 versus 2.3 points, respectively, at week 26 (P = .0002).

In addition, both MG-ADL and QMG scores in the AChR+ subgroup were superior for inebilizumab versus placebo at week 26, with reductions of 4.2 versus 2.4, and 4.4 versus 2.0; P = .0015 and P = .0011, respectively.

In the MuSK+ subgroup, inebilizumab-treated patients had better MG-ADL scores than placebo-treated patients, with reductions of 3.9 versus 1.7 points, respectively, at week 26, although this difference did not meet statistical significance.

“There were no increased safety incidents in the inebilizumab-treated patients versus placebo, and a similar percentage of safety incidents in the AChR–positive and MuSK–positive groups. There were three deaths reported, all likely related to myasthenic crisis,” he said.

Nowak said that inebilizumab is “unique from the other currently FDA-approved medications for myasthenia gravis in that it’s targeting the upstream immunopathogenic mechanism of disease, specifically B cells — and B cells that are actually antibody-secreting cells.”

“It is targeting the factories of autoantibody production, whereas an FcRn antagonist, for example, is not targeting those factories but rather targeting what’s being produced — the immunoglobulins, IgGs in general,” he added.

Nowak said that what is particularly exciting about the drug is that the schedule is not very frequent. It begins with an initial IV infusion, followed by a second infusion 2 weeks later and a third infusion 6 months after that, so that patients are treated approximately every 6 months. This is in contrast to some other targeted therapies, where failing to address the underlying factors driving immunopathogenesis necessitates more regular and frequent medication administration.
 

New, Novel, Exciting

Commenting on the research, Neelam Goyal, MD, who chaired the session, said, “It’s definitely new, novel, interesting, exciting.”

Goyal, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California, also noted that while B-cell depletion has shown some previous success in MG, it was with rituximab, a CD20 B-cell depleting agent.

She noted that unlike rituximab, which targets CD20, inebilizumab targets CD19, although both medications lead to B-cell depletion. Rituximab has proven effective for MUSK–positive MG, which accounts for approximately 5% of cases.

However, Goyal noted that the results for AChR–positive MG have been mixed — “the BeatMG trial was negative and the RINOMAX trial was positive. So, I think this is really interesting. It is exciting, and this drug is already on the market.”

She added that although inebilizumab is already US Food and Drug Administration–approved for the treatment of neuromyelitis optica, it still faces approval and indication hurdles for MG.

The future of this drug in the management algorithm for MG remains uncertain. Goyal noted that it’s “quite costly,” and although its benefits are evident — particularly for FcRn and complement inhibitors — some early data from chimeric antigen receptor T-cell therapy studies appear significantly more impressive.

Nowak disclosed research support from the National Institutes of Health, Genentech, Alexion Pharmaceuticals, argenx, Annexon Biosciences, Ra Pharmaceuticals (now UCB S.A.), the Myasthenia Gravis Foundation of America, Momenta Pharmaceuticals (now Janssen), Immunovant, Grifols, S.A., and Viela Bio, Horizon Therapeutics (now Amgen). Served as a consultant and advisor for Alexion Pharmaceuticals, argenx, Cabaletta Bio, Cour Pharmaceuticals, Ra Pharmaceuticals (now UCB S.A.), Immunovant, Momenta Pharmaceuticals (now Janssen), and Viela Bio (Horizon Therapeutics, now Amgen).

Goyal disclosed consultant, advisory, or grant support from argenx, UCB, Alexion, and Janssen. The study was funded by Amgen.
 

A version of this article appeared on Medscape.com.

Editor’s Note
By Glenn S. Williams
In this year’s Rare Neurological Disease Special Report, we focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust.

A Note From NORD
By Pamela Gavin
Through NORD’s collaboration with Neurology Reviews, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

Genetic Testing for ALS, Now a Standard, Creates a Path Toward Individualized Care
By Ted Bosworth
Overall, there is a sense of progress in ALS. The hope is that clinical research is reaching a tipping point where targeted treatments may offer hope to patients with ALS.

Myasthenia Gravis: Patient Choice, Cultural Change
By John Jesitus
Used appropriately, newer treatments for myasthenia gravis can provide dramatic results faster and more safely than broad immunosuppressants.

Promise for Disease-Modifying Therapies to Tame Huntington’s Disease
By Neil Osterweil
Much progress has been made in managing the symptoms of Huntington’s disease, but the real excitement lies in the development of disease-modifying drugs and genetic therapy.

Diagnosing and Managing Duchenne Muscular Dystrophy: Tips for Practicing Clinicians
By Batya Swift Yasgur, MA, LSW
Healthcare providers should be familiar enough with Duchenne muscular dystrophy to provide timely diagnosis and early intervention as well as practical and emotional support to the patient and family/caregivers.

Neuromyelitis Optica: Historically Misdiagnosed — Now Demands Prompt Treatment
By Kate Johnson
Rapid diagnosis and treatment of NMO “means potentially preventing future devastating neurologic injury.”

Untangling CIDP
By Jennie Smith
Though a preferred biomarker remains elusive, this difficult-to-diagnose neuropathy has seen important recent advances in diagnosis and treatment.

Newborn Screening Programs: What Do Clinicians Need to Know?
By Batya Swift Yasgur, MA, LSW
The goal of newborn screening is to identify babies with genetic disorders who otherwise have no obvious symptoms.

Balancing Act: Weighing the Pros and Cons of Genetic Testing in Rare Diseases
By Frieda Wiley
While genetic testing may offer great potential for providing answers to patients and clinicians seeking insight into a rare disorder, the technology holds some pros and cons that neurologists should be aware of.

Editor’s Note
By Glenn S. Williams
In this year’s Rare Neurological Disease Special Report, we focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust.

A Note From NORD
By Pamela Gavin
Through NORD’s collaboration with Neurology Reviews, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

Genetic Testing for ALS, Now a Standard, Creates a Path Toward Individualized Care
By Ted Bosworth
Overall, there is a sense of progress in ALS. The hope is that clinical research is reaching a tipping point where targeted treatments may offer hope to patients with ALS.

Myasthenia Gravis: Patient Choice, Cultural Change
By John Jesitus
Used appropriately, newer treatments for myasthenia gravis can provide dramatic results faster and more safely than broad immunosuppressants.

Promise for Disease-Modifying Therapies to Tame Huntington’s Disease
By Neil Osterweil
Much progress has been made in managing the symptoms of Huntington’s disease, but the real excitement lies in the development of disease-modifying drugs and genetic therapy.

Diagnosing and Managing Duchenne Muscular Dystrophy: Tips for Practicing Clinicians
By Batya Swift Yasgur, MA, LSW
Healthcare providers should be familiar enough with Duchenne muscular dystrophy to provide timely diagnosis and early intervention as well as practical and emotional support to the patient and family/caregivers.

Neuromyelitis Optica: Historically Misdiagnosed — Now Demands Prompt Treatment
By Kate Johnson
Rapid diagnosis and treatment of NMO “means potentially preventing future devastating neurologic injury.”

Untangling CIDP
By Jennie Smith
Though a preferred biomarker remains elusive, this difficult-to-diagnose neuropathy has seen important recent advances in diagnosis and treatment.

Newborn Screening Programs: What Do Clinicians Need to Know?
By Batya Swift Yasgur, MA, LSW
The goal of newborn screening is to identify babies with genetic disorders who otherwise have no obvious symptoms.

Balancing Act: Weighing the Pros and Cons of Genetic Testing in Rare Diseases
By Frieda Wiley
While genetic testing may offer great potential for providing answers to patients and clinicians seeking insight into a rare disorder, the technology holds some pros and cons that neurologists should be aware of.

Editor’s Note
By Glenn S. Williams
In this year’s Rare Neurological Disease Special Report, we focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust.

A Note From NORD
By Pamela Gavin
Through NORD’s collaboration with Neurology Reviews, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

Genetic Testing for ALS, Now a Standard, Creates a Path Toward Individualized Care
By Ted Bosworth
Overall, there is a sense of progress in ALS. The hope is that clinical research is reaching a tipping point where targeted treatments may offer hope to patients with ALS.

Myasthenia Gravis: Patient Choice, Cultural Change
By John Jesitus
Used appropriately, newer treatments for myasthenia gravis can provide dramatic results faster and more safely than broad immunosuppressants.

Promise for Disease-Modifying Therapies to Tame Huntington’s Disease
By Neil Osterweil
Much progress has been made in managing the symptoms of Huntington’s disease, but the real excitement lies in the development of disease-modifying drugs and genetic therapy.

Diagnosing and Managing Duchenne Muscular Dystrophy: Tips for Practicing Clinicians
By Batya Swift Yasgur, MA, LSW
Healthcare providers should be familiar enough with Duchenne muscular dystrophy to provide timely diagnosis and early intervention as well as practical and emotional support to the patient and family/caregivers.

Neuromyelitis Optica: Historically Misdiagnosed — Now Demands Prompt Treatment
By Kate Johnson
Rapid diagnosis and treatment of NMO “means potentially preventing future devastating neurologic injury.”

Untangling CIDP
By Jennie Smith
Though a preferred biomarker remains elusive, this difficult-to-diagnose neuropathy has seen important recent advances in diagnosis and treatment.

Newborn Screening Programs: What Do Clinicians Need to Know?
By Batya Swift Yasgur, MA, LSW
The goal of newborn screening is to identify babies with genetic disorders who otherwise have no obvious symptoms.

Balancing Act: Weighing the Pros and Cons of Genetic Testing in Rare Diseases
By Frieda Wiley
While genetic testing may offer great potential for providing answers to patients and clinicians seeking insight into a rare disorder, the technology holds some pros and cons that neurologists should be aware of.

Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.

“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

dermatology.cdlib.org/CC BY-SA 3.0/wikimedia

Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
 

Guidelines First Presented in 2022 and Published in 2023

A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.

Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.

But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).

Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.

Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.

Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.

In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.

A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.

The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.

The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
 

Will the Guidelines Lead to Overscreening? 

The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.

“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.

Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.

“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.

“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”

Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.

“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”

He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ” 

The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”

Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”

The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.

A version of this article appeared on Medscape.com.

Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.

“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

dermatology.cdlib.org/CC BY-SA 3.0/wikimedia

Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
 

Guidelines First Presented in 2022 and Published in 2023

A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.

Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.

But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).

Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.

Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.

Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.

In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.

A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.

The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.

The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
 

Will the Guidelines Lead to Overscreening? 

The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.

“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.

Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.

“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.

“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”

Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.

“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”

He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ” 

The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”

Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”

The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.

A version of this article appeared on Medscape.com.

Newly issued guidelines for cancer screening in patients with dermatomyositis had 100% sensitivity in a single institution’s cohort, though most of the cancers found would have been detected with standard cancer screenings recommended for the general population, according to a research letter published in JAMA Dermatology.

“These early results emphasize the continued need to refine risk assessment and cancer screening for patients with dermatomyositis while balancing resource use and outcomes,” concluded Caroline J. Stone and her colleagues at the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

dermatology.cdlib.org/CC BY-SA 3.0/wikimedia

Patients with dermatomyositis have approximately a 4.7 times greater risk for cancer than those without it, according to a 2016 meta-analysis. Despite the well-established link between cancer and dermatomyositis, cancer in people with idiopathic inflammatory myopathies is commonly diagnosed at a later stage and is the leading cause of death in people with these conditions.
 

Guidelines First Presented in 2022 and Published in 2023

A wide variability in screening practices eventually led the International Myositis Assessment & Clinical Studies Group (IMACS) to present the first evidence-based and consensus-based guidelines for cancer screening of patients with idiopathic inflammatory myopathies, including those with dermatomyositis, at the 2022 annual meeting of the American College of Rheumatology and publish them in 2023 in Nature Reviews Rheumatology. The guidelines advise low-risk patients to undergo basic cancer screening with routine blood and urine studies, liver function tests, plain chest radiography, and age- and sex-appropriate cancer screening.

Intermediate- and high-risk patients are recommended to undergo enhanced screening that can include mammography, Pap tests, endoscopy/colonoscopy, pelvic and transvaginal ultrasonography, prostate-specific antigen or cancer antigen 125 blood tests, fecal occult blood tests, and CT of the neck, thorax, abdomen, and pelvis.

But because the guidelines are new, little evidence exists regarding their validation in real-world cohorts. Researchers, therefore, assessed the IMACS guidelines in 370 patients, aged 18-80 years, who visited the University of Pennsylvania rheumatology-dermatology specialty clinic between July 2008 and January 2024. All participants had dermatomyositis and at least 3 years of follow-up and were an average 48 years old. The vast majority were women (87%) and White participants (89%).

Most (68.6%) had myositis-specific autoantibody test results, one of the factors included in the guidelines for determining whether the patient should be classified as low, intermediate, or high risk. Other factors for risk stratification included myositis subtype, age at disease onset, and clinical features. About half (49.2%) had classic dermatomyositis, 42.4% had amyopathic dermatomyositis, 3.8% had juvenile dermatomyositis, 3.2% had hypomyopathic dermatomyositis, 0.8% had antisynthetase syndrome, and 0.5% had immune-mediated necrotizing myopathy.

Just over half the patients (54%) were classified as high risk, while 37.3% were classified as intermediate risk and 8.9% as low risk using the guidelines. Among the 18 patients (4.9%) with paraneoplastic dermatomyositis, 15 were classified as high risk and 3 as intermediate risk.

Of the patients diagnosed with cancer, 55% of cases were diagnosed about a year before their dermatomyositis diagnosis. In three patients, symptoms “suggestive of cancer at the time of dermatomyositis diagnosis, including lymphadenopathy and unexplained weight loss,” led to diagnostic testing that found an underlying cancer.

In the eight patients diagnosed with cancer after their dermatomyositis diagnosis, 75% of the cancers were identified during the first year of follow-up and 25% in the second year. Five were identified based on basic cancer screening and three on enhanced screening.

A total of 11 patients (3%) developed intravenous contrast allergies, and no other adverse events were reported to be associated with cancer screening, but the study was not designed to capture other types of adverse screening effects, such as cost, quality of life, or risk from radiation exposure.

The most common neoplasm identified was breast cancer, found in nine (50%) of the patients using mammography. Two patients had lung cancer identified with chest radiography and two had ovarian cancer identified with abdominal radiography and CT. The remaining five patients included one each with bladder cancer, papillary thyroid cancer, renal cell carcinoma, non-Hodgkin lymphoma, and adenocarcinoma with unknown primary.

The sensitivity of the guidelines in detecting cancer related to dermatomyositis was 100%, though the authors noted that the “IMACS risk-stratification scheme may overestimate cancer risk and encourage enhanced screening protocols of unclear benefit.” Most of the cancers found after dermatomyositis diagnosis were detected with routine age- and sex-related screening that already falls under basic cancer screening recommendations for the general population. Nonetheless, 90% of the participants fell into the intermediate- and high-risk groups, warranting a more comprehensive and costly enhanced screening protocol.
 

Will the Guidelines Lead to Overscreening? 

The 4.9% cancer prevalence is considerably lower than the typical 15%-25% prevalence among patients with dermatomyositis, but the findings, regardless, suggest the guidelines will lead to overscreening, wrote Andrea D. Maderal, MD, University of Miami Miller School of Medicine in Florida, and Alisa Femia, MD, New York University Grossman School of Medicine, New York City, in an accompanying editorial. Given that the median age in patients with cancer in the study was 58 years — 18 years older than the age cutoff for high-risk criteria — one way to refine the guidelines may be to increase the age for the high-risk category, they suggested.

“While these guidelines led to many ultimately unnecessary screening tests based on currently recommended designations of intermediate-risk and high-risk patients, these guidelines reflect a more conservative approach to screening than was previously performed,” Dr. Maderal and Dr. Femia wrote.

Jeff Gehlhausen, MD, PhD, an assistant professor of dermatology at Yale School of Medicine, New Haven, Connecticut, said he is not concerned about overscreening in patients, however, and is “very enthusiastic” about the findings.

“Patients are very anxious for good reason,” given the typical cancer prevalence of 25% in this population, he said in an interview. “I think therein lies the challenge — with that risk, what is ‘enough’ screening?” Yet this “incredibly impressive” study “provides real insights into the applicability of the IMACS screenings to our dermatomyositis management,” including relevance to his own patients. “Their findings are instructive for how to better evaluate these patients in a more mindful fashion,” he said, and they are particularly welcome, given how widely variable practice has historically been before the guidelines were issued.

“This question has been an outstanding one for decades, and nearly every doctor has a different answer,” Dr. Gehlhausen said. “The introduction of the guidelines alone are now much more actionable with this study, and that’s why it’s such an important one for our community.”

Benedict Wu, DO, PhD, director of Inpatient Dermatology and an assistant professor at Montefiore Einstein and a member of the Montefiore Einstein Comprehensive Cancer Center in New York City, similarly regarded the findings as reassuring, though he was surprised at the low prevalence of cancer in the patients.

“The most reassuring finding was that the detection of most malignancies was possible by using routine age- and sex-related screening combined with basic cancer screening,” Wu said in an interview. “Basic cancer screening can reduce costs while keeping patients safe.”

He also found it reassuring that all the paraneoplastic dermatomyositis was in intermediate- or high-risk patients, and while he does not see the IMACS guidelines as overestimating cancer risk, he does think “the risk stratification and recommended screening tests could be revised to be less ‘aggressive.’ ” 

The overall low rate of cancer in the group “calls into question the need for stringent and annual cancer screening,” he said. “In this large cohort of patients, the fact that malignancy was detected within 2 years of dermatomyositis diagnosis will help guide us with long-term screening recommendations.”

Despite the study’s small size and single-center design, the demographics of the patients nearly represents exactly what is found in the United States more broadly, Wu noted. He also drew attention to how many patients lacked the myositis antibody profile performed, and he agreed with the authors that more extensive and prospective studies need to be conducted. He also emphasized the need to keep in mind that “the primary goal of dermatomyositis management should focus on controlling/reducing the disease burden.”

The research was funded by the National Institutes of Health and the US Department of Veterans Affairs. The authors had no disclosures. Dr. Maderal reported personal fees from argenx. No disclosures were noted for Dr. Gehlhausen and Dr. Wu.

A version of this article appeared on Medscape.com.

EDITOR’S NOTE

This year, we again focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust. Let’s hope the work of many dedicated researchers adds to the list of rare neurological diseases for which treatment is available.

This year also marks a change of leadership at NORD, our publishing partner in this annual supplement. We here at Neurology Reviews salute the leadership and accomplishments of former NORD CEO Peter Saltonstall and also welcome incoming CEO Pamela Gavin, who has spent many years in NORD leadership roles and was essential in the planning, launch, and early years of this annual supplement. I can think of no one better than Pamela Gavin to continue NORD’s mission into the future.

And finally, a recap of accolades for this annual supplement. For the second year in a row, the Rare Neurological Disease Special Report has won an Azbee award in the category of annual supplement from the American Society of Business Publication Editors. The 2023 issue won a National Gold Award and a Regional Gold Award.

—Glenn Williams, VP, Group Editor, Neurology Reviews and MDedge Neurology

A NOTE FROM NORD

Hello, and Welcome! The National Organization for Rare Disorders (NORD) is pleased to partner with Neurology Reviews to bring you the 2024 edition of the Rare Neurological Disease Report. Through this collaboration, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

As healthcare providers, you play a key role in catalyzing advancements and bringing new hope and possibilities to the rare disease community. Your efforts can contribute to shortening the diagnostic odyssey and improving day-to-day care for people living with rare disorders in crucial ways:

Identifying patients: Healthcare providers can recognize the possible signs of a rare disease and initiate further investigation or referral to specialists. Early detection is key as it can lead to a quicker, more accurate diagnosis, better management, and improved outcomes.

Educating other physicians: Many rare diseases are not well-known or understood by the general medical community. Healthcare providers can help bridge this knowledge gap by educating other physicians about rare conditions. They can raise awareness through clinical teaching, seminars, medical literature, or continuing medical education (CME) sessions focused on rare diseases. Raising awareness and providing up-to-date information about rare diseases bolsters diagnostic and treatment capabilities within the medical field.

Providing information to patients: Once a rare disease is identified, healthcare providers can offer valuable support to patients and their families. They can provide potential treatments and management strategies. They can also connect patients with support groups, support programs, educational resources, and specialists with expertise in specific rare conditions. Clear communication and guidance on support resources can positively impact patients’ well-being, empower them to make informed decisions, and help them navigate a complex rare condition.

This issue of the Rare Disease Neurological Special Report features articles by rare disease medical experts on specific diseases with updates on clinical management. Topics include the diagnosis and management of Duchenne muscular dystrophy, the promise of disease-modifying therapies for Huntington’s disease, patient choices and cultural changes around myasthenia gravis, advances in neuromyelitis optica, and untangling chronic inflammatory demyelinating polyneuropathy. In addition, two online-only articles offer timely insights from key opinion leaders on the pros and cons of genetic testing and what clinicians need to know about newborn screening.

You will also find information about the NORD Rare Diseases and Orphan Products Breakthrough Summit. This annual event convenes thought leaders from patient advocacy organizations, industry, academia, medical and research institutions, and government to discuss critical topics facing the rare disease community. 

NORD is deeply appreciative of healthcare professionals like you, who despite long hours and demanding workloads, remain committed to staying up to date on the latest medical advances for the benefit of their patients. Your dedication and hard work make a significant difference to the patients and families we serve, and your commitment does not go unnoticed. Thank you for all that you do.

—Pamela Gavin, NORD Chief Executive Officer

EDITOR’S NOTE

This year, we again focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust. Let’s hope the work of many dedicated researchers adds to the list of rare neurological diseases for which treatment is available.

This year also marks a change of leadership at NORD, our publishing partner in this annual supplement. We here at Neurology Reviews salute the leadership and accomplishments of former NORD CEO Peter Saltonstall and also welcome incoming CEO Pamela Gavin, who has spent many years in NORD leadership roles and was essential in the planning, launch, and early years of this annual supplement. I can think of no one better than Pamela Gavin to continue NORD’s mission into the future.

And finally, a recap of accolades for this annual supplement. For the second year in a row, the Rare Neurological Disease Special Report has won an Azbee award in the category of annual supplement from the American Society of Business Publication Editors. The 2023 issue won a National Gold Award and a Regional Gold Award.

—Glenn Williams, VP, Group Editor, Neurology Reviews and MDedge Neurology

A NOTE FROM NORD

Hello, and Welcome! The National Organization for Rare Disorders (NORD) is pleased to partner with Neurology Reviews to bring you the 2024 edition of the Rare Neurological Disease Report. Through this collaboration, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

As healthcare providers, you play a key role in catalyzing advancements and bringing new hope and possibilities to the rare disease community. Your efforts can contribute to shortening the diagnostic odyssey and improving day-to-day care for people living with rare disorders in crucial ways:

Identifying patients: Healthcare providers can recognize the possible signs of a rare disease and initiate further investigation or referral to specialists. Early detection is key as it can lead to a quicker, more accurate diagnosis, better management, and improved outcomes.

Educating other physicians: Many rare diseases are not well-known or understood by the general medical community. Healthcare providers can help bridge this knowledge gap by educating other physicians about rare conditions. They can raise awareness through clinical teaching, seminars, medical literature, or continuing medical education (CME) sessions focused on rare diseases. Raising awareness and providing up-to-date information about rare diseases bolsters diagnostic and treatment capabilities within the medical field.

Providing information to patients: Once a rare disease is identified, healthcare providers can offer valuable support to patients and their families. They can provide potential treatments and management strategies. They can also connect patients with support groups, support programs, educational resources, and specialists with expertise in specific rare conditions. Clear communication and guidance on support resources can positively impact patients’ well-being, empower them to make informed decisions, and help them navigate a complex rare condition.

This issue of the Rare Disease Neurological Special Report features articles by rare disease medical experts on specific diseases with updates on clinical management. Topics include the diagnosis and management of Duchenne muscular dystrophy, the promise of disease-modifying therapies for Huntington’s disease, patient choices and cultural changes around myasthenia gravis, advances in neuromyelitis optica, and untangling chronic inflammatory demyelinating polyneuropathy. In addition, two online-only articles offer timely insights from key opinion leaders on the pros and cons of genetic testing and what clinicians need to know about newborn screening.

You will also find information about the NORD Rare Diseases and Orphan Products Breakthrough Summit. This annual event convenes thought leaders from patient advocacy organizations, industry, academia, medical and research institutions, and government to discuss critical topics facing the rare disease community. 

NORD is deeply appreciative of healthcare professionals like you, who despite long hours and demanding workloads, remain committed to staying up to date on the latest medical advances for the benefit of their patients. Your dedication and hard work make a significant difference to the patients and families we serve, and your commitment does not go unnoticed. Thank you for all that you do.

—Pamela Gavin, NORD Chief Executive Officer

EDITOR’S NOTE

This year, we again focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust. Let’s hope the work of many dedicated researchers adds to the list of rare neurological diseases for which treatment is available.

This year also marks a change of leadership at NORD, our publishing partner in this annual supplement. We here at Neurology Reviews salute the leadership and accomplishments of former NORD CEO Peter Saltonstall and also welcome incoming CEO Pamela Gavin, who has spent many years in NORD leadership roles and was essential in the planning, launch, and early years of this annual supplement. I can think of no one better than Pamela Gavin to continue NORD’s mission into the future.

And finally, a recap of accolades for this annual supplement. For the second year in a row, the Rare Neurological Disease Special Report has won an Azbee award in the category of annual supplement from the American Society of Business Publication Editors. The 2023 issue won a National Gold Award and a Regional Gold Award.

—Glenn Williams, VP, Group Editor, Neurology Reviews and MDedge Neurology

A NOTE FROM NORD

Hello, and Welcome! The National Organization for Rare Disorders (NORD) is pleased to partner with Neurology Reviews to bring you the 2024 edition of the Rare Neurological Disease Report. Through this collaboration, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

As healthcare providers, you play a key role in catalyzing advancements and bringing new hope and possibilities to the rare disease community. Your efforts can contribute to shortening the diagnostic odyssey and improving day-to-day care for people living with rare disorders in crucial ways:

Identifying patients: Healthcare providers can recognize the possible signs of a rare disease and initiate further investigation or referral to specialists. Early detection is key as it can lead to a quicker, more accurate diagnosis, better management, and improved outcomes.

Educating other physicians: Many rare diseases are not well-known or understood by the general medical community. Healthcare providers can help bridge this knowledge gap by educating other physicians about rare conditions. They can raise awareness through clinical teaching, seminars, medical literature, or continuing medical education (CME) sessions focused on rare diseases. Raising awareness and providing up-to-date information about rare diseases bolsters diagnostic and treatment capabilities within the medical field.

Providing information to patients: Once a rare disease is identified, healthcare providers can offer valuable support to patients and their families. They can provide potential treatments and management strategies. They can also connect patients with support groups, support programs, educational resources, and specialists with expertise in specific rare conditions. Clear communication and guidance on support resources can positively impact patients’ well-being, empower them to make informed decisions, and help them navigate a complex rare condition.

This issue of the Rare Disease Neurological Special Report features articles by rare disease medical experts on specific diseases with updates on clinical management. Topics include the diagnosis and management of Duchenne muscular dystrophy, the promise of disease-modifying therapies for Huntington’s disease, patient choices and cultural changes around myasthenia gravis, advances in neuromyelitis optica, and untangling chronic inflammatory demyelinating polyneuropathy. In addition, two online-only articles offer timely insights from key opinion leaders on the pros and cons of genetic testing and what clinicians need to know about newborn screening.

You will also find information about the NORD Rare Diseases and Orphan Products Breakthrough Summit. This annual event convenes thought leaders from patient advocacy organizations, industry, academia, medical and research institutions, and government to discuss critical topics facing the rare disease community. 

NORD is deeply appreciative of healthcare professionals like you, who despite long hours and demanding workloads, remain committed to staying up to date on the latest medical advances for the benefit of their patients. Your dedication and hard work make a significant difference to the patients and families we serve, and your commitment does not go unnoticed. Thank you for all that you do.

—Pamela Gavin, NORD Chief Executive Officer