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Balancing Act: Weighing the Pros and Cons of Genetic Testing in Rare Diseases
The overwhelming majority of rare diseases have a genetic origin, with estimates varying from 71.9% to 80% of rare diseases. Although a rare disease is defined as a condition that affects fewer than 200,000 people domestically, collectively, rare diseases impact approximately 30 million US residents, with at least one of the more than 7,000 rare genetic disorders. In fact, the population of patients with at least one rare disease mirrors the prevalence of people who have type 2 diabetes, or one in every 10 people. Despite their prevalence, most rare conditions are treated only when symptomatic, as many cases remain either misdiagnosed or undiagnosed. As with most health conditions, it is imperative to have a prompt and accurate diagnosis to improve outcomes and avoid inappropriate or unnecessary treatments that may pose severe side effects to the patient.
To that end, this report weighs the less obvious pros and cons of genetic testing in rare diseases of which neurologists should be aware.
The Path to Accurate Diagnosis Remains Long Despite Increased Genetic Testing
When it comes to identifying the greatest challenge in rare genetic disease testing for the neurology community, experts have different opinions. For Kiley Boone Quintana, MD, assistant professor of pediatrics at the University of New Mexico in Albuquerque, the greatest challenge for neurologists navigating this space lies in becoming comfortable with the unknown.
“Many neurologists think genetic testing will certainly find an answer or that the answers will be black and white — which is not true,” said Dr. Quintana. “Instead of clear answers, we often find variants of unknown significance and genetic changes like a deletion or duplication that can have reduced penetrance, so clinicians have to become comfortable with not always having an answer or not knowing exactly how the answer will impact the person.”
One reason for late diagnosis is the need for more knowledge or familiarity a clinician may have with a certain disease, given its rarity.
Perhaps the nebulous nature of genetic testing for people living with rare diseases unveils another drawback, which centers around what researchers refer to as the “diagnostic odyssey.” While the concept describing the average time to diagnosis as 5 years, the time to diagnosis can vary greatly in the rare disease community. In some cases, patients may experience diagnostic delays of only a few months. For others, the time frame could be a decade or greater. The time frame often depends on the patient’s age, phenotype, and accessibility to resources.
Despite these diagnostic challenges, Debra Regier, MD, PhD, chief, genetics and metabolism, at Children’s National Hospital in Washington, DC, sees the silver lining in identifying the underlying cause of a patient’s symptoms of illness. In some cases, a diagnosis leads a patient to access disease-specific medication. However, in the rare genetic disease space, the occurrence is low, as only approximately 10% of these diagnosed conditions have an available treatment.
Despite the small selection of disease-specific therapies for this patient population, patients may still have options, especially when it comes to palliating symptoms.
“We often look toward disease experts to consider what medications are more likely to be supportive,” Dr. Regier said. “This might mean considering a pain regimen, a seizure regimen, other type of symptomatic treatment, or even using some information learned to support the current patient from cases where other families may have preceded them in the odyssey.”
Whole Exome and Whole Genome Testing Continues Growing in Prevalence, But Neither Offers a Panacea
Historically, genetic testing was expensive, with only a few genes interrogated at a time. However, the past decade has seen prices simmer down with the introduction of next-generation sequencing — a technology that improves both the accuracy and utility of genetic testing.
One form of genetic testing, called whole exome sequencing, has proven especially helpful in recent years because it looks at all 20,000 genes and spelling changes that can cause mutations and genetic diseases. However, whole exome testing comes with its own limitations. It tests at the DNA loci that produce the actual protein blueprints but does not look at the DNA between those spaces. In addition, the medical community lacks a comprehensive understanding of all 20,000 genes, as scientists have yet to understand all their functions.
Unfortunately, the drawbacks do not stop there.
“Whole exome sequencing is not good at detecting conditions such as Huntington’s disease or Fragile X syndrome,” Dr. Quintana said. “It also fails to pick up spelling changes in DNA of noncoding regions, which we are learning do have functions in epigenetics.”
Quality also can limit reliability of both exome and genome testing. According to Dr. Regier, trustworthiness of results depends on several factors, including the lab conducting the test and the analysis performed. To help ensure quality, Dr. Regier and her colleagues use only CLIA-certified labs and labs that follow the American College of Medical Genetics (ACMG) guidelines. Furthermore, they allow only qualified experts to analyze the results, experts who hold board certifications with either the American College of Medical Genetics and Genomics or the American Board of Pathology.
Familial and Societal Stigma Surrounding Rare Diseases Engenders Emotional, Psychological, and Financial Distress
Ultimately, traversing the trajectory of delayed diagnosis and its ambiguity also leaves questions regarding how it will impact the person. All too often, these mysteries transcend the patient with the condition, affecting relatives and other loved ones, as the familial and societal stigma surrounding rare diseases engenders emotional and psychological distress.
In cases with prolonged or delayed diagnostics, Dr. Quintana said that neurologists should advise patients to prepare themselves for the potential of arduous workups — some of which may also come at a high price. Not only does a circuitous path to diagnosis impede treatment initiation, but it often results in major trauma for patients and their caregivers, who encounter significant emotional, psychological, and financial distress in the fallout. Emotional distress of misdiagnosis or lack of a diagnosis remains a significant pain point for patients and their family members alike.
Emotional distress presents the greatest drawback for the rare disease community, according to Dr. Regier. She described the cons of navigating a rare genetic disease diagnosis as “very personal” for families.
“Sometimes, there can be guilt or shame associated with a genetic illness,” Dr. Regier noted. “Understanding the ‘why’ or knowing better how to use nonspecific treatments can be incredibly important to reduce guilt and shame, but it also allows the family to feel like there is a reason and encourages inclusion in the social setting.”
Diagnosis typically results in inclusion in a patient and family group, which increases understanding while easing some of the psychological and emotional stress associated with not knowing the cause.
Establishing Social Support Networks Typically Falls on the Patient and Loved Ones
Another con in rare genetic diseases is the lack of adoption across the community.
Because of the long haul, neurologists and other clinicians should recognize the need for patients to have support. Both Dr. Regier and Dr. Quintana agreed that communal support is a critical component of managing the rare genetic disease population. However, finding one’s tribe is easier said than done. Due to the diagnostic hurdles and low number of people with confirmed diagnoses, patient communities and patient advocacy groups for people with individual rare diseases can be underdeveloped. However, the importance of family-based support groups should not be understated. The low community head counts and high level of time investment for care also contributes to poor recruitment turnouts for clinical trials and, subsequently, the sparse number of therapies for such conditions in the pipeline. However, it is also worth noting that, in the case of rare diseases, insufficient disease state knowledge, antiquated policies, lack of funding, and poor research and development diagnostic infrastructure also amplify such cons.
Patients can form communities of support by finding other families and knowing what to expect in terms of complications. While clinicians may not always have the resources to help the patient establish support systems, they can increase the patients’ awareness and encourage them to search for groups that align with their needs. Dr. Quintana reported that many of her patients find support groups of people with the same rare conditions through social media outlets such as Facebook.
Lack of Widespread Genetic Testing Adoption Remains a Barrier in Rare Diseases
As Dr. Quintana told Neurology Reviews, geneticists are more likely to order exome testing, despite the fact that genome-wide testing is slightly more likely to find a diagnosis. However, she anticipates that genome-wide testing will gain wider adoption in the future.
In terms of cost and feasibility, genetic testing can identify roughly 50% of the underlying etiology of a rare disease, including phenotyping to make a clinical diagnosis and using genetic testing, according to Dr. Regier.
Regarding the broad use of whole genome sequencing, Dr. Regier foresees that the more we learn about all the diagnostic and prognostic information rare disease testing can give us, “the more this number will grow.”
As an example of the true impact, she shared how new research indicates that changes to one’s DNA can lead to intellectual disability.
Dr. Quintana agreed that genetic testing will increase, noting an increase in genetic testing ordered from neonatal intensive care units. However, that uptick comes with the caveat of an ever-evolving landscape as genetic companies continue undergoing mergers, acquisitions, and other structural changes that can complicate service availability, provision, and acceptance.
Even if the clinician orders a comprehensive workup, he or she may still encounter resistance at the hands of insurance companies, which can prolong an accurate and prompt diagnosis while hindering families’ access to a thorough investigation.
“Genetic testing is advantageous for insurance companies as well and can prevent unnecessary lab tests to find an answer,” said Dr. Quintana.
Accessibility and Lack of Geneticists Often a Rate-Limiting Step
The paucity of geneticists also creates another hurdle. “Where I practice in New Mexico and in many other places in this country, there’s a shortage of geneticists,” Dr. Quintana said. “For 3 years, the state had only one geneticist, and that’s a lot of ground to cover.”
Dr. Quintana went on to stress the importance of neurologists and other clinicians conducting outreach in rural areas despite the logistical barriers; oftentimes, families cannot travel to big cities. Despite these geographical challenges, prenatal genetic testing is becoming more accessible for both rural and urban areas. For that reason, some babies are born with a diagnosis, allowing the parents and healthcare providers to take immediate action.
Moreover, risks and uncertainty exist around genetic testing results and access to long-term life insurance and disability insurance coverage. “Obtaining proper consent prior to genetic testing is very important,” said Dr. Quintana.
In many cases, genetic counseling may be beneficial because it offers patients some additional information and resources that help them understand not only the results of their genetic tests but also the consequences of their conditions.
Ultimately, Genetic Testing in Rare Diseases Requires All Stakeholders to Have Patience and Tenacity
Dr. Regier summarized some of the nuances of genetic testing in the rare disease community. “Families understand that you might not be able to make the diagnosis,” Dr. Regier said. “It is more important to them that you stay on the journey with them, even if there is not a diagnosis.”
Another critical element of the diagnostic voyage hinges on clinicians recognizing and honoring that every family — and patient — is different.
“Some families want to do testing while others want to take one thing at a time and start with symptom management,” Dr. Regier said. “Both of these approaches are good, and every family has the right to decide when and if genetic testing should be part of their diagnostic odyssey.”
Suggested Reading
Baynam G et al. Stigma Associated With Genetic Testing for Rare Diseases — Causes and Recommendations. Front Genet. 2024 Apr 4:15:1335768. doi: 10.3389/fgene.2024.1335768.
Marwaha S et al. A Guide for the Diagnosis of Rare and Undiagnosed Disease: Beyond the Exome. Genome Med. 2022 Feb 28;14(1):23. doi: 10.1186/s13073-022-01026-w.
The overwhelming majority of rare diseases have a genetic origin, with estimates varying from 71.9% to 80% of rare diseases. Although a rare disease is defined as a condition that affects fewer than 200,000 people domestically, collectively, rare diseases impact approximately 30 million US residents, with at least one of the more than 7,000 rare genetic disorders. In fact, the population of patients with at least one rare disease mirrors the prevalence of people who have type 2 diabetes, or one in every 10 people. Despite their prevalence, most rare conditions are treated only when symptomatic, as many cases remain either misdiagnosed or undiagnosed. As with most health conditions, it is imperative to have a prompt and accurate diagnosis to improve outcomes and avoid inappropriate or unnecessary treatments that may pose severe side effects to the patient.
To that end, this report weighs the less obvious pros and cons of genetic testing in rare diseases of which neurologists should be aware.
The Path to Accurate Diagnosis Remains Long Despite Increased Genetic Testing
When it comes to identifying the greatest challenge in rare genetic disease testing for the neurology community, experts have different opinions. For Kiley Boone Quintana, MD, assistant professor of pediatrics at the University of New Mexico in Albuquerque, the greatest challenge for neurologists navigating this space lies in becoming comfortable with the unknown.
“Many neurologists think genetic testing will certainly find an answer or that the answers will be black and white — which is not true,” said Dr. Quintana. “Instead of clear answers, we often find variants of unknown significance and genetic changes like a deletion or duplication that can have reduced penetrance, so clinicians have to become comfortable with not always having an answer or not knowing exactly how the answer will impact the person.”
One reason for late diagnosis is the need for more knowledge or familiarity a clinician may have with a certain disease, given its rarity.
Perhaps the nebulous nature of genetic testing for people living with rare diseases unveils another drawback, which centers around what researchers refer to as the “diagnostic odyssey.” While the concept describing the average time to diagnosis as 5 years, the time to diagnosis can vary greatly in the rare disease community. In some cases, patients may experience diagnostic delays of only a few months. For others, the time frame could be a decade or greater. The time frame often depends on the patient’s age, phenotype, and accessibility to resources.
Despite these diagnostic challenges, Debra Regier, MD, PhD, chief, genetics and metabolism, at Children’s National Hospital in Washington, DC, sees the silver lining in identifying the underlying cause of a patient’s symptoms of illness. In some cases, a diagnosis leads a patient to access disease-specific medication. However, in the rare genetic disease space, the occurrence is low, as only approximately 10% of these diagnosed conditions have an available treatment.
Despite the small selection of disease-specific therapies for this patient population, patients may still have options, especially when it comes to palliating symptoms.
“We often look toward disease experts to consider what medications are more likely to be supportive,” Dr. Regier said. “This might mean considering a pain regimen, a seizure regimen, other type of symptomatic treatment, or even using some information learned to support the current patient from cases where other families may have preceded them in the odyssey.”
Whole Exome and Whole Genome Testing Continues Growing in Prevalence, But Neither Offers a Panacea
Historically, genetic testing was expensive, with only a few genes interrogated at a time. However, the past decade has seen prices simmer down with the introduction of next-generation sequencing — a technology that improves both the accuracy and utility of genetic testing.
One form of genetic testing, called whole exome sequencing, has proven especially helpful in recent years because it looks at all 20,000 genes and spelling changes that can cause mutations and genetic diseases. However, whole exome testing comes with its own limitations. It tests at the DNA loci that produce the actual protein blueprints but does not look at the DNA between those spaces. In addition, the medical community lacks a comprehensive understanding of all 20,000 genes, as scientists have yet to understand all their functions.
Unfortunately, the drawbacks do not stop there.
“Whole exome sequencing is not good at detecting conditions such as Huntington’s disease or Fragile X syndrome,” Dr. Quintana said. “It also fails to pick up spelling changes in DNA of noncoding regions, which we are learning do have functions in epigenetics.”
Quality also can limit reliability of both exome and genome testing. According to Dr. Regier, trustworthiness of results depends on several factors, including the lab conducting the test and the analysis performed. To help ensure quality, Dr. Regier and her colleagues use only CLIA-certified labs and labs that follow the American College of Medical Genetics (ACMG) guidelines. Furthermore, they allow only qualified experts to analyze the results, experts who hold board certifications with either the American College of Medical Genetics and Genomics or the American Board of Pathology.
Familial and Societal Stigma Surrounding Rare Diseases Engenders Emotional, Psychological, and Financial Distress
Ultimately, traversing the trajectory of delayed diagnosis and its ambiguity also leaves questions regarding how it will impact the person. All too often, these mysteries transcend the patient with the condition, affecting relatives and other loved ones, as the familial and societal stigma surrounding rare diseases engenders emotional and psychological distress.
In cases with prolonged or delayed diagnostics, Dr. Quintana said that neurologists should advise patients to prepare themselves for the potential of arduous workups — some of which may also come at a high price. Not only does a circuitous path to diagnosis impede treatment initiation, but it often results in major trauma for patients and their caregivers, who encounter significant emotional, psychological, and financial distress in the fallout. Emotional distress of misdiagnosis or lack of a diagnosis remains a significant pain point for patients and their family members alike.
Emotional distress presents the greatest drawback for the rare disease community, according to Dr. Regier. She described the cons of navigating a rare genetic disease diagnosis as “very personal” for families.
“Sometimes, there can be guilt or shame associated with a genetic illness,” Dr. Regier noted. “Understanding the ‘why’ or knowing better how to use nonspecific treatments can be incredibly important to reduce guilt and shame, but it also allows the family to feel like there is a reason and encourages inclusion in the social setting.”
Diagnosis typically results in inclusion in a patient and family group, which increases understanding while easing some of the psychological and emotional stress associated with not knowing the cause.
Establishing Social Support Networks Typically Falls on the Patient and Loved Ones
Another con in rare genetic diseases is the lack of adoption across the community.
Because of the long haul, neurologists and other clinicians should recognize the need for patients to have support. Both Dr. Regier and Dr. Quintana agreed that communal support is a critical component of managing the rare genetic disease population. However, finding one’s tribe is easier said than done. Due to the diagnostic hurdles and low number of people with confirmed diagnoses, patient communities and patient advocacy groups for people with individual rare diseases can be underdeveloped. However, the importance of family-based support groups should not be understated. The low community head counts and high level of time investment for care also contributes to poor recruitment turnouts for clinical trials and, subsequently, the sparse number of therapies for such conditions in the pipeline. However, it is also worth noting that, in the case of rare diseases, insufficient disease state knowledge, antiquated policies, lack of funding, and poor research and development diagnostic infrastructure also amplify such cons.
Patients can form communities of support by finding other families and knowing what to expect in terms of complications. While clinicians may not always have the resources to help the patient establish support systems, they can increase the patients’ awareness and encourage them to search for groups that align with their needs. Dr. Quintana reported that many of her patients find support groups of people with the same rare conditions through social media outlets such as Facebook.
Lack of Widespread Genetic Testing Adoption Remains a Barrier in Rare Diseases
As Dr. Quintana told Neurology Reviews, geneticists are more likely to order exome testing, despite the fact that genome-wide testing is slightly more likely to find a diagnosis. However, she anticipates that genome-wide testing will gain wider adoption in the future.
In terms of cost and feasibility, genetic testing can identify roughly 50% of the underlying etiology of a rare disease, including phenotyping to make a clinical diagnosis and using genetic testing, according to Dr. Regier.
Regarding the broad use of whole genome sequencing, Dr. Regier foresees that the more we learn about all the diagnostic and prognostic information rare disease testing can give us, “the more this number will grow.”
As an example of the true impact, she shared how new research indicates that changes to one’s DNA can lead to intellectual disability.
Dr. Quintana agreed that genetic testing will increase, noting an increase in genetic testing ordered from neonatal intensive care units. However, that uptick comes with the caveat of an ever-evolving landscape as genetic companies continue undergoing mergers, acquisitions, and other structural changes that can complicate service availability, provision, and acceptance.
Even if the clinician orders a comprehensive workup, he or she may still encounter resistance at the hands of insurance companies, which can prolong an accurate and prompt diagnosis while hindering families’ access to a thorough investigation.
“Genetic testing is advantageous for insurance companies as well and can prevent unnecessary lab tests to find an answer,” said Dr. Quintana.
Accessibility and Lack of Geneticists Often a Rate-Limiting Step
The paucity of geneticists also creates another hurdle. “Where I practice in New Mexico and in many other places in this country, there’s a shortage of geneticists,” Dr. Quintana said. “For 3 years, the state had only one geneticist, and that’s a lot of ground to cover.”
Dr. Quintana went on to stress the importance of neurologists and other clinicians conducting outreach in rural areas despite the logistical barriers; oftentimes, families cannot travel to big cities. Despite these geographical challenges, prenatal genetic testing is becoming more accessible for both rural and urban areas. For that reason, some babies are born with a diagnosis, allowing the parents and healthcare providers to take immediate action.
Moreover, risks and uncertainty exist around genetic testing results and access to long-term life insurance and disability insurance coverage. “Obtaining proper consent prior to genetic testing is very important,” said Dr. Quintana.
In many cases, genetic counseling may be beneficial because it offers patients some additional information and resources that help them understand not only the results of their genetic tests but also the consequences of their conditions.
Ultimately, Genetic Testing in Rare Diseases Requires All Stakeholders to Have Patience and Tenacity
Dr. Regier summarized some of the nuances of genetic testing in the rare disease community. “Families understand that you might not be able to make the diagnosis,” Dr. Regier said. “It is more important to them that you stay on the journey with them, even if there is not a diagnosis.”
Another critical element of the diagnostic voyage hinges on clinicians recognizing and honoring that every family — and patient — is different.
“Some families want to do testing while others want to take one thing at a time and start with symptom management,” Dr. Regier said. “Both of these approaches are good, and every family has the right to decide when and if genetic testing should be part of their diagnostic odyssey.”
Suggested Reading
Baynam G et al. Stigma Associated With Genetic Testing for Rare Diseases — Causes and Recommendations. Front Genet. 2024 Apr 4:15:1335768. doi: 10.3389/fgene.2024.1335768.
Marwaha S et al. A Guide for the Diagnosis of Rare and Undiagnosed Disease: Beyond the Exome. Genome Med. 2022 Feb 28;14(1):23. doi: 10.1186/s13073-022-01026-w.
The overwhelming majority of rare diseases have a genetic origin, with estimates varying from 71.9% to 80% of rare diseases. Although a rare disease is defined as a condition that affects fewer than 200,000 people domestically, collectively, rare diseases impact approximately 30 million US residents, with at least one of the more than 7,000 rare genetic disorders. In fact, the population of patients with at least one rare disease mirrors the prevalence of people who have type 2 diabetes, or one in every 10 people. Despite their prevalence, most rare conditions are treated only when symptomatic, as many cases remain either misdiagnosed or undiagnosed. As with most health conditions, it is imperative to have a prompt and accurate diagnosis to improve outcomes and avoid inappropriate or unnecessary treatments that may pose severe side effects to the patient.
To that end, this report weighs the less obvious pros and cons of genetic testing in rare diseases of which neurologists should be aware.
The Path to Accurate Diagnosis Remains Long Despite Increased Genetic Testing
When it comes to identifying the greatest challenge in rare genetic disease testing for the neurology community, experts have different opinions. For Kiley Boone Quintana, MD, assistant professor of pediatrics at the University of New Mexico in Albuquerque, the greatest challenge for neurologists navigating this space lies in becoming comfortable with the unknown.
“Many neurologists think genetic testing will certainly find an answer or that the answers will be black and white — which is not true,” said Dr. Quintana. “Instead of clear answers, we often find variants of unknown significance and genetic changes like a deletion or duplication that can have reduced penetrance, so clinicians have to become comfortable with not always having an answer or not knowing exactly how the answer will impact the person.”
One reason for late diagnosis is the need for more knowledge or familiarity a clinician may have with a certain disease, given its rarity.
Perhaps the nebulous nature of genetic testing for people living with rare diseases unveils another drawback, which centers around what researchers refer to as the “diagnostic odyssey.” While the concept describing the average time to diagnosis as 5 years, the time to diagnosis can vary greatly in the rare disease community. In some cases, patients may experience diagnostic delays of only a few months. For others, the time frame could be a decade or greater. The time frame often depends on the patient’s age, phenotype, and accessibility to resources.
Despite these diagnostic challenges, Debra Regier, MD, PhD, chief, genetics and metabolism, at Children’s National Hospital in Washington, DC, sees the silver lining in identifying the underlying cause of a patient’s symptoms of illness. In some cases, a diagnosis leads a patient to access disease-specific medication. However, in the rare genetic disease space, the occurrence is low, as only approximately 10% of these diagnosed conditions have an available treatment.
Despite the small selection of disease-specific therapies for this patient population, patients may still have options, especially when it comes to palliating symptoms.
“We often look toward disease experts to consider what medications are more likely to be supportive,” Dr. Regier said. “This might mean considering a pain regimen, a seizure regimen, other type of symptomatic treatment, or even using some information learned to support the current patient from cases where other families may have preceded them in the odyssey.”
Whole Exome and Whole Genome Testing Continues Growing in Prevalence, But Neither Offers a Panacea
Historically, genetic testing was expensive, with only a few genes interrogated at a time. However, the past decade has seen prices simmer down with the introduction of next-generation sequencing — a technology that improves both the accuracy and utility of genetic testing.
One form of genetic testing, called whole exome sequencing, has proven especially helpful in recent years because it looks at all 20,000 genes and spelling changes that can cause mutations and genetic diseases. However, whole exome testing comes with its own limitations. It tests at the DNA loci that produce the actual protein blueprints but does not look at the DNA between those spaces. In addition, the medical community lacks a comprehensive understanding of all 20,000 genes, as scientists have yet to understand all their functions.
Unfortunately, the drawbacks do not stop there.
“Whole exome sequencing is not good at detecting conditions such as Huntington’s disease or Fragile X syndrome,” Dr. Quintana said. “It also fails to pick up spelling changes in DNA of noncoding regions, which we are learning do have functions in epigenetics.”
Quality also can limit reliability of both exome and genome testing. According to Dr. Regier, trustworthiness of results depends on several factors, including the lab conducting the test and the analysis performed. To help ensure quality, Dr. Regier and her colleagues use only CLIA-certified labs and labs that follow the American College of Medical Genetics (ACMG) guidelines. Furthermore, they allow only qualified experts to analyze the results, experts who hold board certifications with either the American College of Medical Genetics and Genomics or the American Board of Pathology.
Familial and Societal Stigma Surrounding Rare Diseases Engenders Emotional, Psychological, and Financial Distress
Ultimately, traversing the trajectory of delayed diagnosis and its ambiguity also leaves questions regarding how it will impact the person. All too often, these mysteries transcend the patient with the condition, affecting relatives and other loved ones, as the familial and societal stigma surrounding rare diseases engenders emotional and psychological distress.
In cases with prolonged or delayed diagnostics, Dr. Quintana said that neurologists should advise patients to prepare themselves for the potential of arduous workups — some of which may also come at a high price. Not only does a circuitous path to diagnosis impede treatment initiation, but it often results in major trauma for patients and their caregivers, who encounter significant emotional, psychological, and financial distress in the fallout. Emotional distress of misdiagnosis or lack of a diagnosis remains a significant pain point for patients and their family members alike.
Emotional distress presents the greatest drawback for the rare disease community, according to Dr. Regier. She described the cons of navigating a rare genetic disease diagnosis as “very personal” for families.
“Sometimes, there can be guilt or shame associated with a genetic illness,” Dr. Regier noted. “Understanding the ‘why’ or knowing better how to use nonspecific treatments can be incredibly important to reduce guilt and shame, but it also allows the family to feel like there is a reason and encourages inclusion in the social setting.”
Diagnosis typically results in inclusion in a patient and family group, which increases understanding while easing some of the psychological and emotional stress associated with not knowing the cause.
Establishing Social Support Networks Typically Falls on the Patient and Loved Ones
Another con in rare genetic diseases is the lack of adoption across the community.
Because of the long haul, neurologists and other clinicians should recognize the need for patients to have support. Both Dr. Regier and Dr. Quintana agreed that communal support is a critical component of managing the rare genetic disease population. However, finding one’s tribe is easier said than done. Due to the diagnostic hurdles and low number of people with confirmed diagnoses, patient communities and patient advocacy groups for people with individual rare diseases can be underdeveloped. However, the importance of family-based support groups should not be understated. The low community head counts and high level of time investment for care also contributes to poor recruitment turnouts for clinical trials and, subsequently, the sparse number of therapies for such conditions in the pipeline. However, it is also worth noting that, in the case of rare diseases, insufficient disease state knowledge, antiquated policies, lack of funding, and poor research and development diagnostic infrastructure also amplify such cons.
Patients can form communities of support by finding other families and knowing what to expect in terms of complications. While clinicians may not always have the resources to help the patient establish support systems, they can increase the patients’ awareness and encourage them to search for groups that align with their needs. Dr. Quintana reported that many of her patients find support groups of people with the same rare conditions through social media outlets such as Facebook.
Lack of Widespread Genetic Testing Adoption Remains a Barrier in Rare Diseases
As Dr. Quintana told Neurology Reviews, geneticists are more likely to order exome testing, despite the fact that genome-wide testing is slightly more likely to find a diagnosis. However, she anticipates that genome-wide testing will gain wider adoption in the future.
In terms of cost and feasibility, genetic testing can identify roughly 50% of the underlying etiology of a rare disease, including phenotyping to make a clinical diagnosis and using genetic testing, according to Dr. Regier.
Regarding the broad use of whole genome sequencing, Dr. Regier foresees that the more we learn about all the diagnostic and prognostic information rare disease testing can give us, “the more this number will grow.”
As an example of the true impact, she shared how new research indicates that changes to one’s DNA can lead to intellectual disability.
Dr. Quintana agreed that genetic testing will increase, noting an increase in genetic testing ordered from neonatal intensive care units. However, that uptick comes with the caveat of an ever-evolving landscape as genetic companies continue undergoing mergers, acquisitions, and other structural changes that can complicate service availability, provision, and acceptance.
Even if the clinician orders a comprehensive workup, he or she may still encounter resistance at the hands of insurance companies, which can prolong an accurate and prompt diagnosis while hindering families’ access to a thorough investigation.
“Genetic testing is advantageous for insurance companies as well and can prevent unnecessary lab tests to find an answer,” said Dr. Quintana.
Accessibility and Lack of Geneticists Often a Rate-Limiting Step
The paucity of geneticists also creates another hurdle. “Where I practice in New Mexico and in many other places in this country, there’s a shortage of geneticists,” Dr. Quintana said. “For 3 years, the state had only one geneticist, and that’s a lot of ground to cover.”
Dr. Quintana went on to stress the importance of neurologists and other clinicians conducting outreach in rural areas despite the logistical barriers; oftentimes, families cannot travel to big cities. Despite these geographical challenges, prenatal genetic testing is becoming more accessible for both rural and urban areas. For that reason, some babies are born with a diagnosis, allowing the parents and healthcare providers to take immediate action.
Moreover, risks and uncertainty exist around genetic testing results and access to long-term life insurance and disability insurance coverage. “Obtaining proper consent prior to genetic testing is very important,” said Dr. Quintana.
In many cases, genetic counseling may be beneficial because it offers patients some additional information and resources that help them understand not only the results of their genetic tests but also the consequences of their conditions.
Ultimately, Genetic Testing in Rare Diseases Requires All Stakeholders to Have Patience and Tenacity
Dr. Regier summarized some of the nuances of genetic testing in the rare disease community. “Families understand that you might not be able to make the diagnosis,” Dr. Regier said. “It is more important to them that you stay on the journey with them, even if there is not a diagnosis.”
Another critical element of the diagnostic voyage hinges on clinicians recognizing and honoring that every family — and patient — is different.
“Some families want to do testing while others want to take one thing at a time and start with symptom management,” Dr. Regier said. “Both of these approaches are good, and every family has the right to decide when and if genetic testing should be part of their diagnostic odyssey.”
Suggested Reading
Baynam G et al. Stigma Associated With Genetic Testing for Rare Diseases — Causes and Recommendations. Front Genet. 2024 Apr 4:15:1335768. doi: 10.3389/fgene.2024.1335768.
Marwaha S et al. A Guide for the Diagnosis of Rare and Undiagnosed Disease: Beyond the Exome. Genome Med. 2022 Feb 28;14(1):23. doi: 10.1186/s13073-022-01026-w.
Despite ongoing challenges, experts are optimistic about the future of MS therapy
Prior to 1993, a multiple sclerosis (MS) diagnosis could often mean an abbreviated lifespan marked by progressive disability and loss of function. That changed when the Food and Drug Administration approved interferon beta-1b (Betaseron) in 1993, which revolutionized MS therapy and gave hope to the entire MS community.
"The most surprising thing about MS management over the last 30 years is that we’ve been able to treat MS – especially relapsing MS,” said Fred D. Lublin, MD, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in Mount Sinai in New York. “The approval of interferon was a major therapeutic advancement because it was the first treatment for what was an untreatable disease.”
Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center of South Shore Neurologic Associates in Patchogue, N.Y., agrees.
“For people with MS, it’s an extraordinarily lucky and amazingly optimistic time,” he said. “Before interferon beta-1b, MS was called ‘the crippler of young adults’ because more than 50% of these people would require a walker 10 years after diagnosis, and a large number of young and middle-age patients with MS were residing in nursing homes.”
According to Dr. Lublin, the emergence of the immunomodulating therapies placed MS at the leading edge of neurotherapeutics. Interferon beta-1b laid the foundation for new therapies such as another interferon (interferon beta-1a; Avonex), glatiramer acetate (Copaxone), and many other effective therapies with different mechanisms of action. Since the emergence of the first therapy, more than 20 oral and infusion agents with moderate to high efficacy have come to market for relapsing MS.
Treatment options, treatment challenges
Dr. Gudesblatt points out that having numerous therapies from which to choose is both a blessing and a problem.
“The good news is that there are so many options for treating relapsing MS today,” he said. “The bad news is there are so many options. Like doctors who are treating high blood pressure, doctors managing patients with MS often struggle to determine which medication is best for individual patients.”
Despite the promise of vastly better outcomes and prolonged lifespan, MS therapy still faces its share of challenges, including effective therapies for progressive MS and reparative-restorative therapies.
“Choice in route of administration and timing of administration allow for larger and broader discussions to try to meet patients’ needs,” Dr. Lublin said. “We’ve been extremely successful at treating relapses, but not as successful in treating progressive disease.”
The unclear mechanism of pathogenesis amplifies the challenges clinicians face in successful management of patients with MS. For example, experts agree that the therapies for progressive MS have only proven moderately effective at best. The paucity of therapies available for progressive MS and the limitations of the current therapies further limit the outcomes.
Looking ahead
Experts expressed optimistic views about the future of MS therapy as a whole. From Dr. Lublin’s perspective, the MS community stands to gain valuable insights from emerging research focused on treating progressive disease along with new testing to understand the underlying mechanism of progressive disease. Enhanced understanding of the underlying pathogenesis of progressive MS coupled with the ability to diagnose MS – such as improved MRI techniques – have facilitated this process.
Among the therapies with novel mechanisms of action in the pipeline include agents that generate myelin sheath repair. Another potential therapeutic class on the horizon, known as TPK inhibitors, addresses the smoldering of the disease. With these and other therapeutic advances, Dr. Lublin hopes to see better control of progressive disease.
An agenda for the future
In addition, barriers such as access to care, cost, insurance coverage, and tolerance remain ongoing stressors that will likely continue weighing on the MS community and its stakeholders into the future.
Dr. Gudesblatt concluded that advancing MS outcomes in the future hinges on several additional factors.
“We need medicines that are better for relapse and progression; medicines that are better tolerated and safer; and better medicine to address the underlying disease as well as its symptoms. But we also need to appreciate, recognize, and address cognitive impairment along the MS continuum and develop effective reparative options,” he said.
Regardless, he emphasized that these “amazing advancements” in MS therapy have renewed hope that research may identify and expand effective treatments for multiple other neurologic conditions such as muscular dystrophies, neurodegenerative and genetic disorders, movement disorders, and dysautonomia-related diseases. Like MS, all of these conditions have limited therapies, some of which have minimal efficacy. But none of these other disorders has disease-modifying therapies currently available.
‘A beacon of hope’
“MS is the beacon of hope for multiple disease states because it’s cracked the door wide open,” Dr. Gudesblatt said. Relapse no longer gauges the prognosis of today’s MS patient – a prognosis both experts think will only continue to improve with forthcoming innovations.
While the challenges for MS still exist, the bright future that lies ahead may eventually eclipse them.
Prior to 1993, a multiple sclerosis (MS) diagnosis could often mean an abbreviated lifespan marked by progressive disability and loss of function. That changed when the Food and Drug Administration approved interferon beta-1b (Betaseron) in 1993, which revolutionized MS therapy and gave hope to the entire MS community.
"The most surprising thing about MS management over the last 30 years is that we’ve been able to treat MS – especially relapsing MS,” said Fred D. Lublin, MD, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in Mount Sinai in New York. “The approval of interferon was a major therapeutic advancement because it was the first treatment for what was an untreatable disease.”
Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center of South Shore Neurologic Associates in Patchogue, N.Y., agrees.
“For people with MS, it’s an extraordinarily lucky and amazingly optimistic time,” he said. “Before interferon beta-1b, MS was called ‘the crippler of young adults’ because more than 50% of these people would require a walker 10 years after diagnosis, and a large number of young and middle-age patients with MS were residing in nursing homes.”
According to Dr. Lublin, the emergence of the immunomodulating therapies placed MS at the leading edge of neurotherapeutics. Interferon beta-1b laid the foundation for new therapies such as another interferon (interferon beta-1a; Avonex), glatiramer acetate (Copaxone), and many other effective therapies with different mechanisms of action. Since the emergence of the first therapy, more than 20 oral and infusion agents with moderate to high efficacy have come to market for relapsing MS.
Treatment options, treatment challenges
Dr. Gudesblatt points out that having numerous therapies from which to choose is both a blessing and a problem.
“The good news is that there are so many options for treating relapsing MS today,” he said. “The bad news is there are so many options. Like doctors who are treating high blood pressure, doctors managing patients with MS often struggle to determine which medication is best for individual patients.”
Despite the promise of vastly better outcomes and prolonged lifespan, MS therapy still faces its share of challenges, including effective therapies for progressive MS and reparative-restorative therapies.
“Choice in route of administration and timing of administration allow for larger and broader discussions to try to meet patients’ needs,” Dr. Lublin said. “We’ve been extremely successful at treating relapses, but not as successful in treating progressive disease.”
The unclear mechanism of pathogenesis amplifies the challenges clinicians face in successful management of patients with MS. For example, experts agree that the therapies for progressive MS have only proven moderately effective at best. The paucity of therapies available for progressive MS and the limitations of the current therapies further limit the outcomes.
Looking ahead
Experts expressed optimistic views about the future of MS therapy as a whole. From Dr. Lublin’s perspective, the MS community stands to gain valuable insights from emerging research focused on treating progressive disease along with new testing to understand the underlying mechanism of progressive disease. Enhanced understanding of the underlying pathogenesis of progressive MS coupled with the ability to diagnose MS – such as improved MRI techniques – have facilitated this process.
Among the therapies with novel mechanisms of action in the pipeline include agents that generate myelin sheath repair. Another potential therapeutic class on the horizon, known as TPK inhibitors, addresses the smoldering of the disease. With these and other therapeutic advances, Dr. Lublin hopes to see better control of progressive disease.
An agenda for the future
In addition, barriers such as access to care, cost, insurance coverage, and tolerance remain ongoing stressors that will likely continue weighing on the MS community and its stakeholders into the future.
Dr. Gudesblatt concluded that advancing MS outcomes in the future hinges on several additional factors.
“We need medicines that are better for relapse and progression; medicines that are better tolerated and safer; and better medicine to address the underlying disease as well as its symptoms. But we also need to appreciate, recognize, and address cognitive impairment along the MS continuum and develop effective reparative options,” he said.
Regardless, he emphasized that these “amazing advancements” in MS therapy have renewed hope that research may identify and expand effective treatments for multiple other neurologic conditions such as muscular dystrophies, neurodegenerative and genetic disorders, movement disorders, and dysautonomia-related diseases. Like MS, all of these conditions have limited therapies, some of which have minimal efficacy. But none of these other disorders has disease-modifying therapies currently available.
‘A beacon of hope’
“MS is the beacon of hope for multiple disease states because it’s cracked the door wide open,” Dr. Gudesblatt said. Relapse no longer gauges the prognosis of today’s MS patient – a prognosis both experts think will only continue to improve with forthcoming innovations.
While the challenges for MS still exist, the bright future that lies ahead may eventually eclipse them.
Prior to 1993, a multiple sclerosis (MS) diagnosis could often mean an abbreviated lifespan marked by progressive disability and loss of function. That changed when the Food and Drug Administration approved interferon beta-1b (Betaseron) in 1993, which revolutionized MS therapy and gave hope to the entire MS community.
"The most surprising thing about MS management over the last 30 years is that we’ve been able to treat MS – especially relapsing MS,” said Fred D. Lublin, MD, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in Mount Sinai in New York. “The approval of interferon was a major therapeutic advancement because it was the first treatment for what was an untreatable disease.”
Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center of South Shore Neurologic Associates in Patchogue, N.Y., agrees.
“For people with MS, it’s an extraordinarily lucky and amazingly optimistic time,” he said. “Before interferon beta-1b, MS was called ‘the crippler of young adults’ because more than 50% of these people would require a walker 10 years after diagnosis, and a large number of young and middle-age patients with MS were residing in nursing homes.”
According to Dr. Lublin, the emergence of the immunomodulating therapies placed MS at the leading edge of neurotherapeutics. Interferon beta-1b laid the foundation for new therapies such as another interferon (interferon beta-1a; Avonex), glatiramer acetate (Copaxone), and many other effective therapies with different mechanisms of action. Since the emergence of the first therapy, more than 20 oral and infusion agents with moderate to high efficacy have come to market for relapsing MS.
Treatment options, treatment challenges
Dr. Gudesblatt points out that having numerous therapies from which to choose is both a blessing and a problem.
“The good news is that there are so many options for treating relapsing MS today,” he said. “The bad news is there are so many options. Like doctors who are treating high blood pressure, doctors managing patients with MS often struggle to determine which medication is best for individual patients.”
Despite the promise of vastly better outcomes and prolonged lifespan, MS therapy still faces its share of challenges, including effective therapies for progressive MS and reparative-restorative therapies.
“Choice in route of administration and timing of administration allow for larger and broader discussions to try to meet patients’ needs,” Dr. Lublin said. “We’ve been extremely successful at treating relapses, but not as successful in treating progressive disease.”
The unclear mechanism of pathogenesis amplifies the challenges clinicians face in successful management of patients with MS. For example, experts agree that the therapies for progressive MS have only proven moderately effective at best. The paucity of therapies available for progressive MS and the limitations of the current therapies further limit the outcomes.
Looking ahead
Experts expressed optimistic views about the future of MS therapy as a whole. From Dr. Lublin’s perspective, the MS community stands to gain valuable insights from emerging research focused on treating progressive disease along with new testing to understand the underlying mechanism of progressive disease. Enhanced understanding of the underlying pathogenesis of progressive MS coupled with the ability to diagnose MS – such as improved MRI techniques – have facilitated this process.
Among the therapies with novel mechanisms of action in the pipeline include agents that generate myelin sheath repair. Another potential therapeutic class on the horizon, known as TPK inhibitors, addresses the smoldering of the disease. With these and other therapeutic advances, Dr. Lublin hopes to see better control of progressive disease.
An agenda for the future
In addition, barriers such as access to care, cost, insurance coverage, and tolerance remain ongoing stressors that will likely continue weighing on the MS community and its stakeholders into the future.
Dr. Gudesblatt concluded that advancing MS outcomes in the future hinges on several additional factors.
“We need medicines that are better for relapse and progression; medicines that are better tolerated and safer; and better medicine to address the underlying disease as well as its symptoms. But we also need to appreciate, recognize, and address cognitive impairment along the MS continuum and develop effective reparative options,” he said.
Regardless, he emphasized that these “amazing advancements” in MS therapy have renewed hope that research may identify and expand effective treatments for multiple other neurologic conditions such as muscular dystrophies, neurodegenerative and genetic disorders, movement disorders, and dysautonomia-related diseases. Like MS, all of these conditions have limited therapies, some of which have minimal efficacy. But none of these other disorders has disease-modifying therapies currently available.
‘A beacon of hope’
“MS is the beacon of hope for multiple disease states because it’s cracked the door wide open,” Dr. Gudesblatt said. Relapse no longer gauges the prognosis of today’s MS patient – a prognosis both experts think will only continue to improve with forthcoming innovations.
While the challenges for MS still exist, the bright future that lies ahead may eventually eclipse them.
Stroke management: A 30-year retrospective
In 1993, managing patients with stroke had long remained an elusive and somewhat intimidating task for the neurological world. Previous efforts to treat the condition had produced more frustration than success, leaving clinicians and patients alike in despair for a solution. However, some successes in treating coronary thrombosis during that era rejuvenated researchers’ efforts to crack the code. An international team of researchers had studied a Streptococcus derivative (streptokinase) and others had begun to study a natural substance termed tissue plasminogen activator (tPA) as thrombolytic agents to lyse coronary clots and to treat pulmonary embolism. The adverse event of excessive bleeding found in Australian studies done on streptokinase intervention in patients with stroke prompted researchers to contemplate use of tPA in stroke management.
A group of German, Japanese, and American investigators began to research thrombolysis in acute stroke patients during the mid-1980s.
“What was unique is that patients had a CT scan followed by a catheter angiogram,” said Louis Caplan, MD, a senior member of the division of cerebrovascular disease at Beth Israel Deaconess Medical Center, Boston, professor of neurology at Harvard Medical School, Boston, and founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center.
“If they had a blocked vessel, they got the drug, delivered either intravenously or intra-arterially.”
The process involved keeping the catheter open after drug administration to determine whether the vessel had opened or remained occluded. The researchers learned which blocked vessels opened when the drug was given intravenously and which required direct introduction of the drug into the clots.
A group of investigators in the United States funded by the National Institute of Neurological Disease and Stroke then performed a randomized therapeutic trial of intravenous tPA given within 90 minutes and 180 minutes after stroke symptom onset. The study was reported in the New England Journal of Medicine. Soon thereafter, in 1995, the Food and Drug Administration approved the use of tPA following the inclusion and exclusion rules used in the NINDS trial.
After the FDA approved tPA in 1995, stroke management was never the same.
tPA was just one factor in optimizing stroke management
Despite the major therapeutic breakthrough with tPA’s approval, it took the clinics, hospitals, and other acute care systems a while to catch up. “Neurologists and hospitals weren’t ready for acute stroke intervention and proper stroke management in the mid-90s,” Dr. Caplan recalled. “At the time, stroke wasn’t at the forefront of treatment, general neurologists weren’t trained, and there weren’t enough stroke neurologists.”
The preparation and training deficit was further exacerbated by low reimbursement for services. As a result, only about 5% of patients who were eligible for acute stroke management were treated with tPA.
According to Dr. Caplan, during the next 15-20 years, the accumulation of stroke data from MRI and CT vascular imaging clarified further which patients, with what extent of infarction, with which blocked vessels, would be good candidates for treatment.
More patients received interventional treatment using catheters directed into the area of clotting in attempt to remove the blockages. In addition, information regarding intervention at different periods (10-16 hours, up to 24 hours) and conditions (for example, patients with varying degrees of disability, infarct) were tested.
Eventually, hospitals became more attuned to emergency stroke treatment. More neurologists became trained, more stroke centers emerged, and clinicians enjoyed the benefit of technological advancements that allowed them to explore perfusion.
While decentralized care enhances outcomes in stroke management, more progress is needed
As of early 2023, stroke is one of the leading emergency diagnoses, and patients have access to primary and secondary stroke centers that are sprinkled throughout the United States. As impressive as the feat may seem, health care systems still have major strides to make to truly optimize therapy and outcomes in this patient population.
For example, location and access remain important issues. Secondary centers are typically located in large, metropolitan areas. While an urban location makes a primary center geographically more accessible to a larger patient population, traffic frequently hinders door-to-door access.
In the case of rural centers, distance can retard access, but they also face the challenges of how to route patients – especially patients who require more specialized care offered by secondary centers. Fortunately, primary centers have some ways to help better support their patients.
“One thing that happened is that primary centers made agreements with secondary centers via telemedicine to determine whether patients should be treated at the primary center or whether they should be routed to the higher-level center. These arrangements were termed ‘spoke and wheel,’ ” Dr. Caplan told this publication.
However, not all patients who are candidates for transport to a secondary center are able to be transported. In such cases, primary centers can use telemedicine to collaborate with secondary centers for support.
Logistics aside, perhaps today’s greatest challenge for clinicians is ensuring their patients and families receive education to increase their awareness of stroke centers as an important option for treatment and outcome optimization. Many patients and their loved ones do not realize that these centers exist or how to utilize them if and when the time comes.
Right now, some cities have stroke ambulances staffed with physicians to treat patients in the field. This decentralized model helps address access burdens such as door-to-needle delays and transportation while improving survival and recovery. Dr. Caplan said these services are available in Munich, and in a few select U.S. cities such as Cleveland and Houston, which helped pioneer the concept.
Better access in the future?
Looking ahead, Dr. Caplan seems optimistic about how stroke management will continue to evolve. Many cities will have stroke ambulances to provide on-site care, while stroke institutions will improve their cross-collaborative efforts to support their patient populations.
At the crux of cross-collaboration lies enhanced communication between peripheral and urban hospitals.
“Peripheral and urban hospitals and state organizations will engage in smoother integration to figure out when to take patient to the bigger hospitals,” Dr. Caplan said. “I also believe we will see greater emphasis on rehabilitation and recovery.”
As promising as the future looks, only time will tell.
In 1993, managing patients with stroke had long remained an elusive and somewhat intimidating task for the neurological world. Previous efforts to treat the condition had produced more frustration than success, leaving clinicians and patients alike in despair for a solution. However, some successes in treating coronary thrombosis during that era rejuvenated researchers’ efforts to crack the code. An international team of researchers had studied a Streptococcus derivative (streptokinase) and others had begun to study a natural substance termed tissue plasminogen activator (tPA) as thrombolytic agents to lyse coronary clots and to treat pulmonary embolism. The adverse event of excessive bleeding found in Australian studies done on streptokinase intervention in patients with stroke prompted researchers to contemplate use of tPA in stroke management.
A group of German, Japanese, and American investigators began to research thrombolysis in acute stroke patients during the mid-1980s.
“What was unique is that patients had a CT scan followed by a catheter angiogram,” said Louis Caplan, MD, a senior member of the division of cerebrovascular disease at Beth Israel Deaconess Medical Center, Boston, professor of neurology at Harvard Medical School, Boston, and founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center.
“If they had a blocked vessel, they got the drug, delivered either intravenously or intra-arterially.”
The process involved keeping the catheter open after drug administration to determine whether the vessel had opened or remained occluded. The researchers learned which blocked vessels opened when the drug was given intravenously and which required direct introduction of the drug into the clots.
A group of investigators in the United States funded by the National Institute of Neurological Disease and Stroke then performed a randomized therapeutic trial of intravenous tPA given within 90 minutes and 180 minutes after stroke symptom onset. The study was reported in the New England Journal of Medicine. Soon thereafter, in 1995, the Food and Drug Administration approved the use of tPA following the inclusion and exclusion rules used in the NINDS trial.
After the FDA approved tPA in 1995, stroke management was never the same.
tPA was just one factor in optimizing stroke management
Despite the major therapeutic breakthrough with tPA’s approval, it took the clinics, hospitals, and other acute care systems a while to catch up. “Neurologists and hospitals weren’t ready for acute stroke intervention and proper stroke management in the mid-90s,” Dr. Caplan recalled. “At the time, stroke wasn’t at the forefront of treatment, general neurologists weren’t trained, and there weren’t enough stroke neurologists.”
The preparation and training deficit was further exacerbated by low reimbursement for services. As a result, only about 5% of patients who were eligible for acute stroke management were treated with tPA.
According to Dr. Caplan, during the next 15-20 years, the accumulation of stroke data from MRI and CT vascular imaging clarified further which patients, with what extent of infarction, with which blocked vessels, would be good candidates for treatment.
More patients received interventional treatment using catheters directed into the area of clotting in attempt to remove the blockages. In addition, information regarding intervention at different periods (10-16 hours, up to 24 hours) and conditions (for example, patients with varying degrees of disability, infarct) were tested.
Eventually, hospitals became more attuned to emergency stroke treatment. More neurologists became trained, more stroke centers emerged, and clinicians enjoyed the benefit of technological advancements that allowed them to explore perfusion.
While decentralized care enhances outcomes in stroke management, more progress is needed
As of early 2023, stroke is one of the leading emergency diagnoses, and patients have access to primary and secondary stroke centers that are sprinkled throughout the United States. As impressive as the feat may seem, health care systems still have major strides to make to truly optimize therapy and outcomes in this patient population.
For example, location and access remain important issues. Secondary centers are typically located in large, metropolitan areas. While an urban location makes a primary center geographically more accessible to a larger patient population, traffic frequently hinders door-to-door access.
In the case of rural centers, distance can retard access, but they also face the challenges of how to route patients – especially patients who require more specialized care offered by secondary centers. Fortunately, primary centers have some ways to help better support their patients.
“One thing that happened is that primary centers made agreements with secondary centers via telemedicine to determine whether patients should be treated at the primary center or whether they should be routed to the higher-level center. These arrangements were termed ‘spoke and wheel,’ ” Dr. Caplan told this publication.
However, not all patients who are candidates for transport to a secondary center are able to be transported. In such cases, primary centers can use telemedicine to collaborate with secondary centers for support.
Logistics aside, perhaps today’s greatest challenge for clinicians is ensuring their patients and families receive education to increase their awareness of stroke centers as an important option for treatment and outcome optimization. Many patients and their loved ones do not realize that these centers exist or how to utilize them if and when the time comes.
Right now, some cities have stroke ambulances staffed with physicians to treat patients in the field. This decentralized model helps address access burdens such as door-to-needle delays and transportation while improving survival and recovery. Dr. Caplan said these services are available in Munich, and in a few select U.S. cities such as Cleveland and Houston, which helped pioneer the concept.
Better access in the future?
Looking ahead, Dr. Caplan seems optimistic about how stroke management will continue to evolve. Many cities will have stroke ambulances to provide on-site care, while stroke institutions will improve their cross-collaborative efforts to support their patient populations.
At the crux of cross-collaboration lies enhanced communication between peripheral and urban hospitals.
“Peripheral and urban hospitals and state organizations will engage in smoother integration to figure out when to take patient to the bigger hospitals,” Dr. Caplan said. “I also believe we will see greater emphasis on rehabilitation and recovery.”
As promising as the future looks, only time will tell.
In 1993, managing patients with stroke had long remained an elusive and somewhat intimidating task for the neurological world. Previous efforts to treat the condition had produced more frustration than success, leaving clinicians and patients alike in despair for a solution. However, some successes in treating coronary thrombosis during that era rejuvenated researchers’ efforts to crack the code. An international team of researchers had studied a Streptococcus derivative (streptokinase) and others had begun to study a natural substance termed tissue plasminogen activator (tPA) as thrombolytic agents to lyse coronary clots and to treat pulmonary embolism. The adverse event of excessive bleeding found in Australian studies done on streptokinase intervention in patients with stroke prompted researchers to contemplate use of tPA in stroke management.
A group of German, Japanese, and American investigators began to research thrombolysis in acute stroke patients during the mid-1980s.
“What was unique is that patients had a CT scan followed by a catheter angiogram,” said Louis Caplan, MD, a senior member of the division of cerebrovascular disease at Beth Israel Deaconess Medical Center, Boston, professor of neurology at Harvard Medical School, Boston, and founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center.
“If they had a blocked vessel, they got the drug, delivered either intravenously or intra-arterially.”
The process involved keeping the catheter open after drug administration to determine whether the vessel had opened or remained occluded. The researchers learned which blocked vessels opened when the drug was given intravenously and which required direct introduction of the drug into the clots.
A group of investigators in the United States funded by the National Institute of Neurological Disease and Stroke then performed a randomized therapeutic trial of intravenous tPA given within 90 minutes and 180 minutes after stroke symptom onset. The study was reported in the New England Journal of Medicine. Soon thereafter, in 1995, the Food and Drug Administration approved the use of tPA following the inclusion and exclusion rules used in the NINDS trial.
After the FDA approved tPA in 1995, stroke management was never the same.
tPA was just one factor in optimizing stroke management
Despite the major therapeutic breakthrough with tPA’s approval, it took the clinics, hospitals, and other acute care systems a while to catch up. “Neurologists and hospitals weren’t ready for acute stroke intervention and proper stroke management in the mid-90s,” Dr. Caplan recalled. “At the time, stroke wasn’t at the forefront of treatment, general neurologists weren’t trained, and there weren’t enough stroke neurologists.”
The preparation and training deficit was further exacerbated by low reimbursement for services. As a result, only about 5% of patients who were eligible for acute stroke management were treated with tPA.
According to Dr. Caplan, during the next 15-20 years, the accumulation of stroke data from MRI and CT vascular imaging clarified further which patients, with what extent of infarction, with which blocked vessels, would be good candidates for treatment.
More patients received interventional treatment using catheters directed into the area of clotting in attempt to remove the blockages. In addition, information regarding intervention at different periods (10-16 hours, up to 24 hours) and conditions (for example, patients with varying degrees of disability, infarct) were tested.
Eventually, hospitals became more attuned to emergency stroke treatment. More neurologists became trained, more stroke centers emerged, and clinicians enjoyed the benefit of technological advancements that allowed them to explore perfusion.
While decentralized care enhances outcomes in stroke management, more progress is needed
As of early 2023, stroke is one of the leading emergency diagnoses, and patients have access to primary and secondary stroke centers that are sprinkled throughout the United States. As impressive as the feat may seem, health care systems still have major strides to make to truly optimize therapy and outcomes in this patient population.
For example, location and access remain important issues. Secondary centers are typically located in large, metropolitan areas. While an urban location makes a primary center geographically more accessible to a larger patient population, traffic frequently hinders door-to-door access.
In the case of rural centers, distance can retard access, but they also face the challenges of how to route patients – especially patients who require more specialized care offered by secondary centers. Fortunately, primary centers have some ways to help better support their patients.
“One thing that happened is that primary centers made agreements with secondary centers via telemedicine to determine whether patients should be treated at the primary center or whether they should be routed to the higher-level center. These arrangements were termed ‘spoke and wheel,’ ” Dr. Caplan told this publication.
However, not all patients who are candidates for transport to a secondary center are able to be transported. In such cases, primary centers can use telemedicine to collaborate with secondary centers for support.
Logistics aside, perhaps today’s greatest challenge for clinicians is ensuring their patients and families receive education to increase their awareness of stroke centers as an important option for treatment and outcome optimization. Many patients and their loved ones do not realize that these centers exist or how to utilize them if and when the time comes.
Right now, some cities have stroke ambulances staffed with physicians to treat patients in the field. This decentralized model helps address access burdens such as door-to-needle delays and transportation while improving survival and recovery. Dr. Caplan said these services are available in Munich, and in a few select U.S. cities such as Cleveland and Houston, which helped pioneer the concept.
Better access in the future?
Looking ahead, Dr. Caplan seems optimistic about how stroke management will continue to evolve. Many cities will have stroke ambulances to provide on-site care, while stroke institutions will improve their cross-collaborative efforts to support their patient populations.
At the crux of cross-collaboration lies enhanced communication between peripheral and urban hospitals.
“Peripheral and urban hospitals and state organizations will engage in smoother integration to figure out when to take patient to the bigger hospitals,” Dr. Caplan said. “I also believe we will see greater emphasis on rehabilitation and recovery.”
As promising as the future looks, only time will tell.
Race, ethnicity, and socioeconomics are often barriers to migraine care
, according to a study published in the April issue of Headache. People of African descent and Latinx ethnicity tend to fare worse than other people of color and their White counterparts.
“It should be shocking to neurologists and other clinicians who care for migraine patients how few are able to successfully traverse the barriers to achieve an accurate diagnosis and proper, evidence-based, acute and preventative treatment,” commented Peter McAllister, MD, medical director at the New England Institute for Neurology and Headache and chief medical officer for clinical research at Ki Clinical Research in Stamford, Conn. Dr. McAllister was not involved in this study.
Assessing barriers to care
Researchers designed the study with the primary objective of estimating the number of patients with migraines with unmet clinical needs and who were impacted by four preidentified barriers to care. To evaluate their objective, researchers conducted a longitudinal, Internet-based survey known as the Chronic Migraine Epidemiology and Outcomes (CaMEO) study. They collected data over 1 year examining a cohort of patients that mimicked the diverse demographics of the U.S. population. Researchers conducted longitudinal assessments every 3 months for 15 months, incorporating cross-sectional analyses that surveyed health care use, family burden, and comorbidities or endophenotypes.
Eligible enrollees were 18 years of age or older.
Researchers identified four barriers that hindered patient outcomes, and they served as the primary outcomes of the studies. They were:
- Health care provider consultations. Investigators used study participants’ responses to the following question during their interactions with their health care providers to help evaluate the quality of their consultation experience: “What type of doctor is currently managing your headaches?” Researchers included data from patients whose practitioners fit the description of those they deemed best suited to address ongoing headache challenges. These medical professionals included general practitioners, family physicians, internal medicine doctors, nurse practitioners, physician assistants, neurologists, pain specialists, headache specialists, and obstetrician-gynecologists.
- Diagnosis. Carefully evaluating patients’ responses to a series of questions helped researchers gauge the accuracy of diagnosis. Questions included: “Have you ever been diagnosed by a doctor or other health professional with any of the following types of headaches?” Respondents were also given a list of options that provided additional context around their headaches and were encouraged to select all appropriate responses. The list included a fictional response option of “citrene headache” to determine incorrect responses. For this study, researchers deemed it necessary to recognize a chronic migraine diagnosis to ensure that patients received appropriate treatment.
- Minimally appropriate pharmacologic treatment. Researchers used the following question to determine whether patients’ chronic migraine and episodic migraine were being managed with the least amount of pharmacological treatment necessary. “Which of these medications (if any) are you currently using (or typically keep on hand) to treat your headaches when you have them?” Researchers defined “minimally appropriate acute pharmacologic treatment” as the use of any prescription nonsteroidal anti-inflammatory drug (NSAID), triptan, ergotamine derivative, or isometheptene.
- Avoidance of medication overuse. The study authors pointed out the sometimes nebulous process of characterizing the appropriate use of preventative medication in patients with episodic migraines as “not straightforward” for some patients because not all patients require preventive treatment. Study participants were required to report having received any form of preventative therapy, defined as pharmacological therapies approved by guidelines and supported by data. Such therapies included various antiseizure medication, antidepressants (for example, doxepin, venlafaxine, duloxetine, amitriptyline, imipramine, nortriptyline, and desvenlafaxine), antihypertensives, and toxin injections. Treatments such as behavioral and neuromodulatory therapies were excluded from the list.
According to lead author Dawn C. Buse, PhD, of the department of neurology at Albert Einstein College of Medicine, New York, acute medication overuse provides an important modifiable target for intervention and recommends that clinicians use the opportunity to optimize migraine care by reducing the patients’ reliance on acute therapies. Taking such initiatives to decrease medication overuse is especially important in communities of color, who are more likely to overuse medications for migraines.
Patients with higher income levels were more likely to overcome each barrier. People of African, African American, or multiracial descent were more prone to overuse of medications to manage their migraines.
Of the 489,537 respondents invited to participate in the CaMEO study, 16,879 qualified for inclusion. Slightly more than half of the respondents (n = 9,184 [54.7%]) had a migraine-related disability (MIDAS) score of 6 or greater – an indicator of disability that is least mild in nature. Most patients who had episodic migraines or chronic migraines (86.2%) had some form of health insurance coverage (n = 9.184; 84.1%; P = .048). Of those patients who were insured, 7,930 patients experienced episodic migraine (86.3%) and the remainder had chronic migraine (n = 1,254; 13.7%). Higher-income patients were more likely to traverse barriers to care. While patients of African descent had higher consultation rates, they also had higher rates of acute medication overuse.
Patients with chronic migraine were more likely to be older than patients with episodic migraine (41.0 vs. 39.6 years; P = .0001) and female (83.0% vs. 79.0%; P = .001), and White (84.5% vs. 79.1%; P < .001). Similarly, patients with chronic migraine were more likely to have a higher mean body mass index (29.8 kg/m2 vs. 28.9 kg/m2; P < .001) and lower rates of full- or part-time employment (56.8% vs. 67.1%; P < .001), and were less likely to have a 4-year degree (64.8 vs. 55.6; P < .001) and annual household incomes below $75,000 (72.6% vs. 64.6%; P < .001). Approximately three-quarters of the patients with episodic migraine (75.7%; 1655/2187) and one-third of patients with chronic migraine (32.8%; 168/512) received accurate diagnoses.
The data uncovered an association with acute medication overuse. Among current consulters who had received an accurate diagnosis and minimally adequate treatment, medication overuse rates were highest among those reporting two or more races (53%) and Blacks and African Americans (45%) and lowest among Whites (33%) and those categorized as “other” race (32%). Ethnic and cultural differences in headache literacy may contribute to differences in medication overuse.
Strategies to improve outcomes
Both Dr. Buse and Dr. McAllister see the value advocacy and education offer in helping to improve outcomes in marginalized communities and other groups negatively impacted by various barriers.
“Patient advocacy and outreach are key here, especially in those traditionally underrepresented in the migraine space, such as men, people of color, blue-collar workers, etc.,” Dr. McAllister noted.
Dr. Buse emphasized the importance of education for patients and health care professionals alike. “A large percentage of people who meet criteria for migraine in the U.S. do not seek care or possibly even know that they have migraines,” Dr. Buse said. “This finding underscores the importance of public health education about migraine as well as well as providing migraine support, education, and resources to health care professionals on the front lines.”
Other strategies recommended by Dr, Buse to ease the impact of barriers include encouraging patient discussion, setting up time for follow-up appointments and education, referring patients for neurological and other specialty consults when warranted, reviewing essential lifestyle habits for migraine management, and creating personalized, mutually agreed-upon treatment plans.
Dr. Buse has received support and honoraria from AbbVie, Amgen, Avanir, Biohaven, Eli Lilly, and Promius.
, according to a study published in the April issue of Headache. People of African descent and Latinx ethnicity tend to fare worse than other people of color and their White counterparts.
“It should be shocking to neurologists and other clinicians who care for migraine patients how few are able to successfully traverse the barriers to achieve an accurate diagnosis and proper, evidence-based, acute and preventative treatment,” commented Peter McAllister, MD, medical director at the New England Institute for Neurology and Headache and chief medical officer for clinical research at Ki Clinical Research in Stamford, Conn. Dr. McAllister was not involved in this study.
Assessing barriers to care
Researchers designed the study with the primary objective of estimating the number of patients with migraines with unmet clinical needs and who were impacted by four preidentified barriers to care. To evaluate their objective, researchers conducted a longitudinal, Internet-based survey known as the Chronic Migraine Epidemiology and Outcomes (CaMEO) study. They collected data over 1 year examining a cohort of patients that mimicked the diverse demographics of the U.S. population. Researchers conducted longitudinal assessments every 3 months for 15 months, incorporating cross-sectional analyses that surveyed health care use, family burden, and comorbidities or endophenotypes.
Eligible enrollees were 18 years of age or older.
Researchers identified four barriers that hindered patient outcomes, and they served as the primary outcomes of the studies. They were:
- Health care provider consultations. Investigators used study participants’ responses to the following question during their interactions with their health care providers to help evaluate the quality of their consultation experience: “What type of doctor is currently managing your headaches?” Researchers included data from patients whose practitioners fit the description of those they deemed best suited to address ongoing headache challenges. These medical professionals included general practitioners, family physicians, internal medicine doctors, nurse practitioners, physician assistants, neurologists, pain specialists, headache specialists, and obstetrician-gynecologists.
- Diagnosis. Carefully evaluating patients’ responses to a series of questions helped researchers gauge the accuracy of diagnosis. Questions included: “Have you ever been diagnosed by a doctor or other health professional with any of the following types of headaches?” Respondents were also given a list of options that provided additional context around their headaches and were encouraged to select all appropriate responses. The list included a fictional response option of “citrene headache” to determine incorrect responses. For this study, researchers deemed it necessary to recognize a chronic migraine diagnosis to ensure that patients received appropriate treatment.
- Minimally appropriate pharmacologic treatment. Researchers used the following question to determine whether patients’ chronic migraine and episodic migraine were being managed with the least amount of pharmacological treatment necessary. “Which of these medications (if any) are you currently using (or typically keep on hand) to treat your headaches when you have them?” Researchers defined “minimally appropriate acute pharmacologic treatment” as the use of any prescription nonsteroidal anti-inflammatory drug (NSAID), triptan, ergotamine derivative, or isometheptene.
- Avoidance of medication overuse. The study authors pointed out the sometimes nebulous process of characterizing the appropriate use of preventative medication in patients with episodic migraines as “not straightforward” for some patients because not all patients require preventive treatment. Study participants were required to report having received any form of preventative therapy, defined as pharmacological therapies approved by guidelines and supported by data. Such therapies included various antiseizure medication, antidepressants (for example, doxepin, venlafaxine, duloxetine, amitriptyline, imipramine, nortriptyline, and desvenlafaxine), antihypertensives, and toxin injections. Treatments such as behavioral and neuromodulatory therapies were excluded from the list.
According to lead author Dawn C. Buse, PhD, of the department of neurology at Albert Einstein College of Medicine, New York, acute medication overuse provides an important modifiable target for intervention and recommends that clinicians use the opportunity to optimize migraine care by reducing the patients’ reliance on acute therapies. Taking such initiatives to decrease medication overuse is especially important in communities of color, who are more likely to overuse medications for migraines.
Patients with higher income levels were more likely to overcome each barrier. People of African, African American, or multiracial descent were more prone to overuse of medications to manage their migraines.
Of the 489,537 respondents invited to participate in the CaMEO study, 16,879 qualified for inclusion. Slightly more than half of the respondents (n = 9,184 [54.7%]) had a migraine-related disability (MIDAS) score of 6 or greater – an indicator of disability that is least mild in nature. Most patients who had episodic migraines or chronic migraines (86.2%) had some form of health insurance coverage (n = 9.184; 84.1%; P = .048). Of those patients who were insured, 7,930 patients experienced episodic migraine (86.3%) and the remainder had chronic migraine (n = 1,254; 13.7%). Higher-income patients were more likely to traverse barriers to care. While patients of African descent had higher consultation rates, they also had higher rates of acute medication overuse.
Patients with chronic migraine were more likely to be older than patients with episodic migraine (41.0 vs. 39.6 years; P = .0001) and female (83.0% vs. 79.0%; P = .001), and White (84.5% vs. 79.1%; P < .001). Similarly, patients with chronic migraine were more likely to have a higher mean body mass index (29.8 kg/m2 vs. 28.9 kg/m2; P < .001) and lower rates of full- or part-time employment (56.8% vs. 67.1%; P < .001), and were less likely to have a 4-year degree (64.8 vs. 55.6; P < .001) and annual household incomes below $75,000 (72.6% vs. 64.6%; P < .001). Approximately three-quarters of the patients with episodic migraine (75.7%; 1655/2187) and one-third of patients with chronic migraine (32.8%; 168/512) received accurate diagnoses.
The data uncovered an association with acute medication overuse. Among current consulters who had received an accurate diagnosis and minimally adequate treatment, medication overuse rates were highest among those reporting two or more races (53%) and Blacks and African Americans (45%) and lowest among Whites (33%) and those categorized as “other” race (32%). Ethnic and cultural differences in headache literacy may contribute to differences in medication overuse.
Strategies to improve outcomes
Both Dr. Buse and Dr. McAllister see the value advocacy and education offer in helping to improve outcomes in marginalized communities and other groups negatively impacted by various barriers.
“Patient advocacy and outreach are key here, especially in those traditionally underrepresented in the migraine space, such as men, people of color, blue-collar workers, etc.,” Dr. McAllister noted.
Dr. Buse emphasized the importance of education for patients and health care professionals alike. “A large percentage of people who meet criteria for migraine in the U.S. do not seek care or possibly even know that they have migraines,” Dr. Buse said. “This finding underscores the importance of public health education about migraine as well as well as providing migraine support, education, and resources to health care professionals on the front lines.”
Other strategies recommended by Dr, Buse to ease the impact of barriers include encouraging patient discussion, setting up time for follow-up appointments and education, referring patients for neurological and other specialty consults when warranted, reviewing essential lifestyle habits for migraine management, and creating personalized, mutually agreed-upon treatment plans.
Dr. Buse has received support and honoraria from AbbVie, Amgen, Avanir, Biohaven, Eli Lilly, and Promius.
, according to a study published in the April issue of Headache. People of African descent and Latinx ethnicity tend to fare worse than other people of color and their White counterparts.
“It should be shocking to neurologists and other clinicians who care for migraine patients how few are able to successfully traverse the barriers to achieve an accurate diagnosis and proper, evidence-based, acute and preventative treatment,” commented Peter McAllister, MD, medical director at the New England Institute for Neurology and Headache and chief medical officer for clinical research at Ki Clinical Research in Stamford, Conn. Dr. McAllister was not involved in this study.
Assessing barriers to care
Researchers designed the study with the primary objective of estimating the number of patients with migraines with unmet clinical needs and who were impacted by four preidentified barriers to care. To evaluate their objective, researchers conducted a longitudinal, Internet-based survey known as the Chronic Migraine Epidemiology and Outcomes (CaMEO) study. They collected data over 1 year examining a cohort of patients that mimicked the diverse demographics of the U.S. population. Researchers conducted longitudinal assessments every 3 months for 15 months, incorporating cross-sectional analyses that surveyed health care use, family burden, and comorbidities or endophenotypes.
Eligible enrollees were 18 years of age or older.
Researchers identified four barriers that hindered patient outcomes, and they served as the primary outcomes of the studies. They were:
- Health care provider consultations. Investigators used study participants’ responses to the following question during their interactions with their health care providers to help evaluate the quality of their consultation experience: “What type of doctor is currently managing your headaches?” Researchers included data from patients whose practitioners fit the description of those they deemed best suited to address ongoing headache challenges. These medical professionals included general practitioners, family physicians, internal medicine doctors, nurse practitioners, physician assistants, neurologists, pain specialists, headache specialists, and obstetrician-gynecologists.
- Diagnosis. Carefully evaluating patients’ responses to a series of questions helped researchers gauge the accuracy of diagnosis. Questions included: “Have you ever been diagnosed by a doctor or other health professional with any of the following types of headaches?” Respondents were also given a list of options that provided additional context around their headaches and were encouraged to select all appropriate responses. The list included a fictional response option of “citrene headache” to determine incorrect responses. For this study, researchers deemed it necessary to recognize a chronic migraine diagnosis to ensure that patients received appropriate treatment.
- Minimally appropriate pharmacologic treatment. Researchers used the following question to determine whether patients’ chronic migraine and episodic migraine were being managed with the least amount of pharmacological treatment necessary. “Which of these medications (if any) are you currently using (or typically keep on hand) to treat your headaches when you have them?” Researchers defined “minimally appropriate acute pharmacologic treatment” as the use of any prescription nonsteroidal anti-inflammatory drug (NSAID), triptan, ergotamine derivative, or isometheptene.
- Avoidance of medication overuse. The study authors pointed out the sometimes nebulous process of characterizing the appropriate use of preventative medication in patients with episodic migraines as “not straightforward” for some patients because not all patients require preventive treatment. Study participants were required to report having received any form of preventative therapy, defined as pharmacological therapies approved by guidelines and supported by data. Such therapies included various antiseizure medication, antidepressants (for example, doxepin, venlafaxine, duloxetine, amitriptyline, imipramine, nortriptyline, and desvenlafaxine), antihypertensives, and toxin injections. Treatments such as behavioral and neuromodulatory therapies were excluded from the list.
According to lead author Dawn C. Buse, PhD, of the department of neurology at Albert Einstein College of Medicine, New York, acute medication overuse provides an important modifiable target for intervention and recommends that clinicians use the opportunity to optimize migraine care by reducing the patients’ reliance on acute therapies. Taking such initiatives to decrease medication overuse is especially important in communities of color, who are more likely to overuse medications for migraines.
Patients with higher income levels were more likely to overcome each barrier. People of African, African American, or multiracial descent were more prone to overuse of medications to manage their migraines.
Of the 489,537 respondents invited to participate in the CaMEO study, 16,879 qualified for inclusion. Slightly more than half of the respondents (n = 9,184 [54.7%]) had a migraine-related disability (MIDAS) score of 6 or greater – an indicator of disability that is least mild in nature. Most patients who had episodic migraines or chronic migraines (86.2%) had some form of health insurance coverage (n = 9.184; 84.1%; P = .048). Of those patients who were insured, 7,930 patients experienced episodic migraine (86.3%) and the remainder had chronic migraine (n = 1,254; 13.7%). Higher-income patients were more likely to traverse barriers to care. While patients of African descent had higher consultation rates, they also had higher rates of acute medication overuse.
Patients with chronic migraine were more likely to be older than patients with episodic migraine (41.0 vs. 39.6 years; P = .0001) and female (83.0% vs. 79.0%; P = .001), and White (84.5% vs. 79.1%; P < .001). Similarly, patients with chronic migraine were more likely to have a higher mean body mass index (29.8 kg/m2 vs. 28.9 kg/m2; P < .001) and lower rates of full- or part-time employment (56.8% vs. 67.1%; P < .001), and were less likely to have a 4-year degree (64.8 vs. 55.6; P < .001) and annual household incomes below $75,000 (72.6% vs. 64.6%; P < .001). Approximately three-quarters of the patients with episodic migraine (75.7%; 1655/2187) and one-third of patients with chronic migraine (32.8%; 168/512) received accurate diagnoses.
The data uncovered an association with acute medication overuse. Among current consulters who had received an accurate diagnosis and minimally adequate treatment, medication overuse rates were highest among those reporting two or more races (53%) and Blacks and African Americans (45%) and lowest among Whites (33%) and those categorized as “other” race (32%). Ethnic and cultural differences in headache literacy may contribute to differences in medication overuse.
Strategies to improve outcomes
Both Dr. Buse and Dr. McAllister see the value advocacy and education offer in helping to improve outcomes in marginalized communities and other groups negatively impacted by various barriers.
“Patient advocacy and outreach are key here, especially in those traditionally underrepresented in the migraine space, such as men, people of color, blue-collar workers, etc.,” Dr. McAllister noted.
Dr. Buse emphasized the importance of education for patients and health care professionals alike. “A large percentage of people who meet criteria for migraine in the U.S. do not seek care or possibly even know that they have migraines,” Dr. Buse said. “This finding underscores the importance of public health education about migraine as well as well as providing migraine support, education, and resources to health care professionals on the front lines.”
Other strategies recommended by Dr, Buse to ease the impact of barriers include encouraging patient discussion, setting up time for follow-up appointments and education, referring patients for neurological and other specialty consults when warranted, reviewing essential lifestyle habits for migraine management, and creating personalized, mutually agreed-upon treatment plans.
Dr. Buse has received support and honoraria from AbbVie, Amgen, Avanir, Biohaven, Eli Lilly, and Promius.
FROM HEADACHE
Ubrogepant safety and efficacy not affected by triptan therapy
according to a study published in Headache.
“The goal is to get migraine attacks under control as quickly as you can with as few adverse events as possible,” said lead author Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad, California. “Ubrogepant is very efficacious and well tolerated because it has few adverse events.”
Migraine disorder is the third most prevalent disease, and at least one person living in 25% of all U.S. households has the condition.
Clinicians have a wide range of medications at their disposal to treat migraines. These drug classes include triptans, ditans, NSAIDs, dihydroergotamine, and combination analgesics. Although numerous pharmacologic options are available to manage this patient population, an estimated 95% of patients who take oral medications to alleviate their migraine symptoms still fail to achieve relief with at least one acute episode.
Triptans remain a common option and first-line choice for acute migraine relief, but poor tolerability, among other factors, continue to limit their effectiveness. Moreover, their vasoconstrictive properties preclude their use in specific patient populations, such as those who have hypertension, peripheral vascular disease, and cerebral vascular accident. These circumstances, combined with other unmet clinical needs in migraine, have prompted researchers to explore new options, including a newer class of drugs – CGRP receptor antagonists. An endogenous protein, CGRP, has inflammatory and pronociceptive properties that play an active role in contributing to migraine pathogenesis.
Efficacy analyzed by triptan response
To investigate the effects of anti-CGRP treatment in patients with migraine who have a previous history of triptan use, researchers conducted two phase 3, randomized, double-blind, multicenter, single-attack trials, known as ACHIEVE I and ACHIEVE II.
Trial participants ranged in age from 18 to 75 years with a documented history of migraines with or without aura. In ACHIEVE I, investigators randomized 1,327 participants 1:1:1 to receive placebo, ubrogepant 50 mg, or ubrogepant 100 mg and placebo. Randomized patients in ACHIEVE II (n = 1,355) received placebo, ubrogepant 25 mg, or ubrogepant 50 mg to treat a single episode. During the screening process, researchers further placed patients in one of three groups based on their previous triptan use – triptan responder, triptan-insufficient responder, and triptan naive. Patients were further randomized based on their previous experience with triptans and whether they currently used them for migraine prevention. Patients participating in the study had up to 60 days to treat one qualifying migraine of moderate or severe nature at home.
The studies had two primary endpoints. The first was freedom from pain at the 2-hour mark following the initial dose, defined as decreased headache severity from moderate or severe at baseline to no pain. The other primary endpoint was the absence of most bothersome migraine-associated symptom (MBS) – photophobia, phonophobia, or nausea – 2 hours after the initial ubrogepant dose.
The pooled analysis collated data from 1,799 patients in both studies (placebo, n = 912; ubrogepant 50 mg, n = 887). Patients fell into the following categories: 682 triptan responders (placebo, n = 350; ubrogepant, n = 332); 451 triptan-insufficient responders (placebo, n = 223; ubrogepant, n = 228), and 666 triptan naive (placebo, n = 339; ubrogepant, n = 337).
Based on the data, approximately 25% of the patients enrolled in the study fell into the triptan-insufficient category. Of this subpopulation, about 80% of the patients in each treatment group experienced insufficient efficacy when using triptans. In each treatment group of insufficient responders, approximately 17% of patients cited tolerability issues, and 3% had contraindications that precluded them from triptan therapy.
The incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs did not differ appreciably across historical triptan experience subgroups. The highest percentage of participants experiencing a treatment-related TEAE in the pooled ubrogepant 50-mg treatment group was found in the triptan-insufficient responders (10.4%), whereas the highest percentage in the placebo group was found in the triptan-naive subgroup (9.7%). No serious AEs (SAEs) were reported in any subgroup.
The researchers concluded that “ubrogepant efficacy and tolerability did not differ for the acute treatment of migraine in participants classified as triptan responders, triptan-insufficient responders, and triptan naive based on their historical experience with triptans.”
Payers limit use
Despite the promising data, payer hurdles limit ubrogepant’s use, said Stewart Tepper, MD, who was asked to comment on the study. Dr. Tepper, a professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., was not involved in the study. “The study shows that ubrogepant will work as well as those who have not responded well to triptans, which is key,” Dr. Tepper said. “However, payers have set up step edits in which patients aren’t allowed to get ubrogepant unless they fail therapy with at least two triptans.”
Dr. Blumenfeld discounts the rationale behind requiring patients to try a second triptan after failing initial triptan therapy. “There are plenty of studies showing that if you fail one triptan, you’re likely to fail another,” he said. “Why would you put the patient on a different triptan when you could switch them to another drug with a different mechanism of action?”
The results showed that more patients in the ubrogepant 50-mg arm achieved pain freedom than those in the placebo arm within 2 hours after the initial dose in each group.
“Migraine is a very disabling condition, so you want to get the attack under control as quickly as possible while limiting the risk for potential side effects,” said Dr. Blumenfeld. “Ubrogepant is very efficacious and with very few adverse effects, but its use is limited because insurance companies require the failure of several triptans.”
One limitation of the study is that it is a subanalysis.
Dr. Blumenfeld has disclosed advisory board service, consulting, speaking, and authorship for AbbVie, Alder, Amgen, Biohaven, Lilly, Novartis, Teva, Theranica, and Zoscano.
according to a study published in Headache.
“The goal is to get migraine attacks under control as quickly as you can with as few adverse events as possible,” said lead author Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad, California. “Ubrogepant is very efficacious and well tolerated because it has few adverse events.”
Migraine disorder is the third most prevalent disease, and at least one person living in 25% of all U.S. households has the condition.
Clinicians have a wide range of medications at their disposal to treat migraines. These drug classes include triptans, ditans, NSAIDs, dihydroergotamine, and combination analgesics. Although numerous pharmacologic options are available to manage this patient population, an estimated 95% of patients who take oral medications to alleviate their migraine symptoms still fail to achieve relief with at least one acute episode.
Triptans remain a common option and first-line choice for acute migraine relief, but poor tolerability, among other factors, continue to limit their effectiveness. Moreover, their vasoconstrictive properties preclude their use in specific patient populations, such as those who have hypertension, peripheral vascular disease, and cerebral vascular accident. These circumstances, combined with other unmet clinical needs in migraine, have prompted researchers to explore new options, including a newer class of drugs – CGRP receptor antagonists. An endogenous protein, CGRP, has inflammatory and pronociceptive properties that play an active role in contributing to migraine pathogenesis.
Efficacy analyzed by triptan response
To investigate the effects of anti-CGRP treatment in patients with migraine who have a previous history of triptan use, researchers conducted two phase 3, randomized, double-blind, multicenter, single-attack trials, known as ACHIEVE I and ACHIEVE II.
Trial participants ranged in age from 18 to 75 years with a documented history of migraines with or without aura. In ACHIEVE I, investigators randomized 1,327 participants 1:1:1 to receive placebo, ubrogepant 50 mg, or ubrogepant 100 mg and placebo. Randomized patients in ACHIEVE II (n = 1,355) received placebo, ubrogepant 25 mg, or ubrogepant 50 mg to treat a single episode. During the screening process, researchers further placed patients in one of three groups based on their previous triptan use – triptan responder, triptan-insufficient responder, and triptan naive. Patients were further randomized based on their previous experience with triptans and whether they currently used them for migraine prevention. Patients participating in the study had up to 60 days to treat one qualifying migraine of moderate or severe nature at home.
The studies had two primary endpoints. The first was freedom from pain at the 2-hour mark following the initial dose, defined as decreased headache severity from moderate or severe at baseline to no pain. The other primary endpoint was the absence of most bothersome migraine-associated symptom (MBS) – photophobia, phonophobia, or nausea – 2 hours after the initial ubrogepant dose.
The pooled analysis collated data from 1,799 patients in both studies (placebo, n = 912; ubrogepant 50 mg, n = 887). Patients fell into the following categories: 682 triptan responders (placebo, n = 350; ubrogepant, n = 332); 451 triptan-insufficient responders (placebo, n = 223; ubrogepant, n = 228), and 666 triptan naive (placebo, n = 339; ubrogepant, n = 337).
Based on the data, approximately 25% of the patients enrolled in the study fell into the triptan-insufficient category. Of this subpopulation, about 80% of the patients in each treatment group experienced insufficient efficacy when using triptans. In each treatment group of insufficient responders, approximately 17% of patients cited tolerability issues, and 3% had contraindications that precluded them from triptan therapy.
The incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs did not differ appreciably across historical triptan experience subgroups. The highest percentage of participants experiencing a treatment-related TEAE in the pooled ubrogepant 50-mg treatment group was found in the triptan-insufficient responders (10.4%), whereas the highest percentage in the placebo group was found in the triptan-naive subgroup (9.7%). No serious AEs (SAEs) were reported in any subgroup.
The researchers concluded that “ubrogepant efficacy and tolerability did not differ for the acute treatment of migraine in participants classified as triptan responders, triptan-insufficient responders, and triptan naive based on their historical experience with triptans.”
Payers limit use
Despite the promising data, payer hurdles limit ubrogepant’s use, said Stewart Tepper, MD, who was asked to comment on the study. Dr. Tepper, a professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., was not involved in the study. “The study shows that ubrogepant will work as well as those who have not responded well to triptans, which is key,” Dr. Tepper said. “However, payers have set up step edits in which patients aren’t allowed to get ubrogepant unless they fail therapy with at least two triptans.”
Dr. Blumenfeld discounts the rationale behind requiring patients to try a second triptan after failing initial triptan therapy. “There are plenty of studies showing that if you fail one triptan, you’re likely to fail another,” he said. “Why would you put the patient on a different triptan when you could switch them to another drug with a different mechanism of action?”
The results showed that more patients in the ubrogepant 50-mg arm achieved pain freedom than those in the placebo arm within 2 hours after the initial dose in each group.
“Migraine is a very disabling condition, so you want to get the attack under control as quickly as possible while limiting the risk for potential side effects,” said Dr. Blumenfeld. “Ubrogepant is very efficacious and with very few adverse effects, but its use is limited because insurance companies require the failure of several triptans.”
One limitation of the study is that it is a subanalysis.
Dr. Blumenfeld has disclosed advisory board service, consulting, speaking, and authorship for AbbVie, Alder, Amgen, Biohaven, Lilly, Novartis, Teva, Theranica, and Zoscano.
according to a study published in Headache.
“The goal is to get migraine attacks under control as quickly as you can with as few adverse events as possible,” said lead author Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad, California. “Ubrogepant is very efficacious and well tolerated because it has few adverse events.”
Migraine disorder is the third most prevalent disease, and at least one person living in 25% of all U.S. households has the condition.
Clinicians have a wide range of medications at their disposal to treat migraines. These drug classes include triptans, ditans, NSAIDs, dihydroergotamine, and combination analgesics. Although numerous pharmacologic options are available to manage this patient population, an estimated 95% of patients who take oral medications to alleviate their migraine symptoms still fail to achieve relief with at least one acute episode.
Triptans remain a common option and first-line choice for acute migraine relief, but poor tolerability, among other factors, continue to limit their effectiveness. Moreover, their vasoconstrictive properties preclude their use in specific patient populations, such as those who have hypertension, peripheral vascular disease, and cerebral vascular accident. These circumstances, combined with other unmet clinical needs in migraine, have prompted researchers to explore new options, including a newer class of drugs – CGRP receptor antagonists. An endogenous protein, CGRP, has inflammatory and pronociceptive properties that play an active role in contributing to migraine pathogenesis.
Efficacy analyzed by triptan response
To investigate the effects of anti-CGRP treatment in patients with migraine who have a previous history of triptan use, researchers conducted two phase 3, randomized, double-blind, multicenter, single-attack trials, known as ACHIEVE I and ACHIEVE II.
Trial participants ranged in age from 18 to 75 years with a documented history of migraines with or without aura. In ACHIEVE I, investigators randomized 1,327 participants 1:1:1 to receive placebo, ubrogepant 50 mg, or ubrogepant 100 mg and placebo. Randomized patients in ACHIEVE II (n = 1,355) received placebo, ubrogepant 25 mg, or ubrogepant 50 mg to treat a single episode. During the screening process, researchers further placed patients in one of three groups based on their previous triptan use – triptan responder, triptan-insufficient responder, and triptan naive. Patients were further randomized based on their previous experience with triptans and whether they currently used them for migraine prevention. Patients participating in the study had up to 60 days to treat one qualifying migraine of moderate or severe nature at home.
The studies had two primary endpoints. The first was freedom from pain at the 2-hour mark following the initial dose, defined as decreased headache severity from moderate or severe at baseline to no pain. The other primary endpoint was the absence of most bothersome migraine-associated symptom (MBS) – photophobia, phonophobia, or nausea – 2 hours after the initial ubrogepant dose.
The pooled analysis collated data from 1,799 patients in both studies (placebo, n = 912; ubrogepant 50 mg, n = 887). Patients fell into the following categories: 682 triptan responders (placebo, n = 350; ubrogepant, n = 332); 451 triptan-insufficient responders (placebo, n = 223; ubrogepant, n = 228), and 666 triptan naive (placebo, n = 339; ubrogepant, n = 337).
Based on the data, approximately 25% of the patients enrolled in the study fell into the triptan-insufficient category. Of this subpopulation, about 80% of the patients in each treatment group experienced insufficient efficacy when using triptans. In each treatment group of insufficient responders, approximately 17% of patients cited tolerability issues, and 3% had contraindications that precluded them from triptan therapy.
The incidence of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs did not differ appreciably across historical triptan experience subgroups. The highest percentage of participants experiencing a treatment-related TEAE in the pooled ubrogepant 50-mg treatment group was found in the triptan-insufficient responders (10.4%), whereas the highest percentage in the placebo group was found in the triptan-naive subgroup (9.7%). No serious AEs (SAEs) were reported in any subgroup.
The researchers concluded that “ubrogepant efficacy and tolerability did not differ for the acute treatment of migraine in participants classified as triptan responders, triptan-insufficient responders, and triptan naive based on their historical experience with triptans.”
Payers limit use
Despite the promising data, payer hurdles limit ubrogepant’s use, said Stewart Tepper, MD, who was asked to comment on the study. Dr. Tepper, a professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., was not involved in the study. “The study shows that ubrogepant will work as well as those who have not responded well to triptans, which is key,” Dr. Tepper said. “However, payers have set up step edits in which patients aren’t allowed to get ubrogepant unless they fail therapy with at least two triptans.”
Dr. Blumenfeld discounts the rationale behind requiring patients to try a second triptan after failing initial triptan therapy. “There are plenty of studies showing that if you fail one triptan, you’re likely to fail another,” he said. “Why would you put the patient on a different triptan when you could switch them to another drug with a different mechanism of action?”
The results showed that more patients in the ubrogepant 50-mg arm achieved pain freedom than those in the placebo arm within 2 hours after the initial dose in each group.
“Migraine is a very disabling condition, so you want to get the attack under control as quickly as possible while limiting the risk for potential side effects,” said Dr. Blumenfeld. “Ubrogepant is very efficacious and with very few adverse effects, but its use is limited because insurance companies require the failure of several triptans.”
One limitation of the study is that it is a subanalysis.
Dr. Blumenfeld has disclosed advisory board service, consulting, speaking, and authorship for AbbVie, Alder, Amgen, Biohaven, Lilly, Novartis, Teva, Theranica, and Zoscano.
FROM HEADACHE
Adherence and discontinuation limit triptan outcomes
a new Danish study shows.
“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”
Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.
Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
25 years of triptan use
Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.
Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).
Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.
Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.
The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.
Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.
One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.
“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.
“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.
Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.
a new Danish study shows.
“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”
Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.
Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
25 years of triptan use
Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.
Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).
Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.
Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.
The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.
Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.
One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.
“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.
“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.
Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.
a new Danish study shows.
“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”
Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.
Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
25 years of triptan use
Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.
Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).
Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.
Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.
The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.
Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.
One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.
“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.
“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.
Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.
FROM CEPHALALGIA
New sickle cell drugs give hope, but access remains a barrier
Sickle cell disease (SCD) is an incurable genetic blood disorder that reduces patients’ lifespan and quality of life. Many patients live into their 40s or 50s. Yet, throughout their lives, patients are plagued by lethargy, unpredictable painful crises, and frequent hospitalizations. For nearly 20 years, clinicians only had one drug to treat SCD. Since 2017, three new drugs have been approved, but their costs and lack of long-term data have spawned questions regarding access and benefit.
“SCD reduces lifespan by 30 years, and that’s very hard to quantify,” says Ifeyinwa Osunkwo, MD, professor of medicine and pediatrics and director of Sickle Cell Disease Enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, N.C. “If you put a dollar amount on what someone would make working for 30 adult years, that would be more reflective of the true cost of treating the disease.”
In 1984, hydroxyurea (Hydrea, Droxia) became the first drug to treat SCD in adults.
Originally developed as a myelosuppressive antineoplastic, hydroxyurea is used to treat resistant chronic myeloid leukemia and certain head and neck cancers. In SCD, it increases levels of hemoglobin and fetal hemoglobin.
Despite its benefit, hydroxyurea has two major drawbacks: It is only effective in two genotypes – HbSS or HbS/Beta0thal.
HbSS or HbS/Beta0thal genotypes account for 60% of the SCD population, but further studies are required to elucidate hydroxyurea’s effect in other forms of SCD, according to Dr. Osunkwo.
Secondly, hydroxyurea only reduces the frequency of painful episodes by 50% – not enough to ameliorate the pain, said John J. Strouse, MD, associate professor of medicine at Duke University School of Medicine.
Newer therapies offer the potential to enhance the effects of hydroxyurea when used concomitantly. They also give clinicians additional options for patients who either fail hydroxyurea therapy or for whom it is inappropriate.
The amino acid L-glutamine (Endari) became the second drug approved for sickle cell in 2017. Indicated for patients 5 years of age and older, Dr. Osunkwo says many patients were thrilled to have a nonchemotherapeutic option available. However, the medical community received the drug with some skepticism. “The data show Endari is moderately effective at best,” said Dr. Strouse. “Also, the mechanism of action is unclear.”
Additionally, the drug’s powder form and twice-daily dosing regimen make adherence more challenging than swallowing a few hydroxyurea tablets or capsules once a day. In Dr. Osunkwo’s experience, patients who respond best to Endari tend to be those who are naturally motivated individuals who are intentional in their efforts at optimizing their nutrition and self-care.
“It takes a lot to be adherent to Endari,” she said. “You have to work at it.”
On Nov. 15, 2019, the FDA approved crizanlizumab-tmca (Adakveo) for patients 16 years of age and older to decrease the occurrence of vasoocclusive crises.
The drug works by blocking selectin – a protein involved in the painful vascular pathophysiology. Patients receive a loading dose of 5 mg/kg administered via intravenous infusion over 30 minutes at the initiation of therapy, as well as weeks 2 and 4. After that, patients undergo treatment once a month. Nausea, back pain, pyrexia, and arthralgia are the most frequently reported adverse reactions. Clinicians must monitor patients for signs and symptoms of infusion-related reactions.
Ten days later, the FDA approved voxelotor (Oxbryta) for patients ages 12 years and up. The drug inhibits hemoglobin S polymerization and increases hemoglobin levels. Like hydroxyurea, the drug offers the convenience of once-daily dosing, and the tablet can be taken without regard to food. The drug dose requires adjustment for patients with severe hepatic impairment. Headache, fatigue, rash, and gastrointestinal disturbances such as diarrhea, nausea, and abdominal pain fall among the most commonly reported side effects.
Endari, Adakveo, and Oxbryta can all be used as monotherapy. They also provide additional benefits in reducing pain and hospitalizations and improving anemia when used concomitantly with hydroxyurea.
Like so many drugs, these novel therapies are expensive. The cost of these novel treatments has raised some eyebrows.
Annual costs of generic hydroxyurea range in the neighborhood of $1,200. In a 2017 CNBC interview, Endari manufacturer Emmaus stated that it aimed to keep drug costs under $20,000 a year. Annual costs for Adakveo and Oxbryta costs are in the neighborhood of $100,000. Adakveo manufacturer Novartis reportedly priced vials at $2,347. Most patients will require at least three of the maximum four vials per treatment. In a press release, Global Therapeutics stated that Oxbyta would cost $10,417 a month.
However, Dr. Osunkwo says the benefits of these new drugs far exceed the costs from both monetary and quality of life standpoints.
“Sickle cell disease is costly to manage,” she said in an interview. “One hospitalization can cost $10,000.”
Additionally, many SCD patients are publicly insured because of the profound disability and loss of productive work they encounter as a direct consequence of their disease and its complications. Those too sick to complete their high school and postsecondary education find limited employment opportunities.
Those fortunate enough to secure employment face significantly fewer years they can work because their pain, fatigue, frequent hospitalizations, and cumulative organ damage result in permanent disability. Only a smaller number of patients with less severe disease manifestations can secure steady employment and pursue careers that allow them to obtain private insurance.
Even if the newer therapies can help cut some costs, clinicians should be aware that prior authorizations can delay patient access to Adakveo and Oxbyta.
“We wrote the first prescription for Oxbryta in November of 2019, but the prior authorization wasn’t approved until February of 2020,” she said. Adding Adakveo to her institution’s formulary required several months of navigation. Given the arduous process, Dr. Osunkwo anticipates it will take at least year after approval before Adakveo is available for all eligible patients.
The long-term impact of these drugs also remains to be seen, so hydroxyurea will likely remain the drug of choice for many patients, according to Dr. Strouse.
Dr. Osunkwo believes SCD needs more drugs in order to truly optimize outcomes, contain costs, and enhance the patient experience.
Dr. Osunkwo reports consultancy and being on the speaker’s bureau and participating in the advisory board for Novartis, which markets Adakveo, and relationships with a variety of other pharmaceutical companies. She is the editor in chief for Hematology News. Dr. Strouse reports consultancy for Global Therapeutics, which markets Oxbryta.
Sickle cell disease (SCD) is an incurable genetic blood disorder that reduces patients’ lifespan and quality of life. Many patients live into their 40s or 50s. Yet, throughout their lives, patients are plagued by lethargy, unpredictable painful crises, and frequent hospitalizations. For nearly 20 years, clinicians only had one drug to treat SCD. Since 2017, three new drugs have been approved, but their costs and lack of long-term data have spawned questions regarding access and benefit.
“SCD reduces lifespan by 30 years, and that’s very hard to quantify,” says Ifeyinwa Osunkwo, MD, professor of medicine and pediatrics and director of Sickle Cell Disease Enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, N.C. “If you put a dollar amount on what someone would make working for 30 adult years, that would be more reflective of the true cost of treating the disease.”
In 1984, hydroxyurea (Hydrea, Droxia) became the first drug to treat SCD in adults.
Originally developed as a myelosuppressive antineoplastic, hydroxyurea is used to treat resistant chronic myeloid leukemia and certain head and neck cancers. In SCD, it increases levels of hemoglobin and fetal hemoglobin.
Despite its benefit, hydroxyurea has two major drawbacks: It is only effective in two genotypes – HbSS or HbS/Beta0thal.
HbSS or HbS/Beta0thal genotypes account for 60% of the SCD population, but further studies are required to elucidate hydroxyurea’s effect in other forms of SCD, according to Dr. Osunkwo.
Secondly, hydroxyurea only reduces the frequency of painful episodes by 50% – not enough to ameliorate the pain, said John J. Strouse, MD, associate professor of medicine at Duke University School of Medicine.
Newer therapies offer the potential to enhance the effects of hydroxyurea when used concomitantly. They also give clinicians additional options for patients who either fail hydroxyurea therapy or for whom it is inappropriate.
The amino acid L-glutamine (Endari) became the second drug approved for sickle cell in 2017. Indicated for patients 5 years of age and older, Dr. Osunkwo says many patients were thrilled to have a nonchemotherapeutic option available. However, the medical community received the drug with some skepticism. “The data show Endari is moderately effective at best,” said Dr. Strouse. “Also, the mechanism of action is unclear.”
Additionally, the drug’s powder form and twice-daily dosing regimen make adherence more challenging than swallowing a few hydroxyurea tablets or capsules once a day. In Dr. Osunkwo’s experience, patients who respond best to Endari tend to be those who are naturally motivated individuals who are intentional in their efforts at optimizing their nutrition and self-care.
“It takes a lot to be adherent to Endari,” she said. “You have to work at it.”
On Nov. 15, 2019, the FDA approved crizanlizumab-tmca (Adakveo) for patients 16 years of age and older to decrease the occurrence of vasoocclusive crises.
The drug works by blocking selectin – a protein involved in the painful vascular pathophysiology. Patients receive a loading dose of 5 mg/kg administered via intravenous infusion over 30 minutes at the initiation of therapy, as well as weeks 2 and 4. After that, patients undergo treatment once a month. Nausea, back pain, pyrexia, and arthralgia are the most frequently reported adverse reactions. Clinicians must monitor patients for signs and symptoms of infusion-related reactions.
Ten days later, the FDA approved voxelotor (Oxbryta) for patients ages 12 years and up. The drug inhibits hemoglobin S polymerization and increases hemoglobin levels. Like hydroxyurea, the drug offers the convenience of once-daily dosing, and the tablet can be taken without regard to food. The drug dose requires adjustment for patients with severe hepatic impairment. Headache, fatigue, rash, and gastrointestinal disturbances such as diarrhea, nausea, and abdominal pain fall among the most commonly reported side effects.
Endari, Adakveo, and Oxbryta can all be used as monotherapy. They also provide additional benefits in reducing pain and hospitalizations and improving anemia when used concomitantly with hydroxyurea.
Like so many drugs, these novel therapies are expensive. The cost of these novel treatments has raised some eyebrows.
Annual costs of generic hydroxyurea range in the neighborhood of $1,200. In a 2017 CNBC interview, Endari manufacturer Emmaus stated that it aimed to keep drug costs under $20,000 a year. Annual costs for Adakveo and Oxbryta costs are in the neighborhood of $100,000. Adakveo manufacturer Novartis reportedly priced vials at $2,347. Most patients will require at least three of the maximum four vials per treatment. In a press release, Global Therapeutics stated that Oxbyta would cost $10,417 a month.
However, Dr. Osunkwo says the benefits of these new drugs far exceed the costs from both monetary and quality of life standpoints.
“Sickle cell disease is costly to manage,” she said in an interview. “One hospitalization can cost $10,000.”
Additionally, many SCD patients are publicly insured because of the profound disability and loss of productive work they encounter as a direct consequence of their disease and its complications. Those too sick to complete their high school and postsecondary education find limited employment opportunities.
Those fortunate enough to secure employment face significantly fewer years they can work because their pain, fatigue, frequent hospitalizations, and cumulative organ damage result in permanent disability. Only a smaller number of patients with less severe disease manifestations can secure steady employment and pursue careers that allow them to obtain private insurance.
Even if the newer therapies can help cut some costs, clinicians should be aware that prior authorizations can delay patient access to Adakveo and Oxbyta.
“We wrote the first prescription for Oxbryta in November of 2019, but the prior authorization wasn’t approved until February of 2020,” she said. Adding Adakveo to her institution’s formulary required several months of navigation. Given the arduous process, Dr. Osunkwo anticipates it will take at least year after approval before Adakveo is available for all eligible patients.
The long-term impact of these drugs also remains to be seen, so hydroxyurea will likely remain the drug of choice for many patients, according to Dr. Strouse.
Dr. Osunkwo believes SCD needs more drugs in order to truly optimize outcomes, contain costs, and enhance the patient experience.
Dr. Osunkwo reports consultancy and being on the speaker’s bureau and participating in the advisory board for Novartis, which markets Adakveo, and relationships with a variety of other pharmaceutical companies. She is the editor in chief for Hematology News. Dr. Strouse reports consultancy for Global Therapeutics, which markets Oxbryta.
Sickle cell disease (SCD) is an incurable genetic blood disorder that reduces patients’ lifespan and quality of life. Many patients live into their 40s or 50s. Yet, throughout their lives, patients are plagued by lethargy, unpredictable painful crises, and frequent hospitalizations. For nearly 20 years, clinicians only had one drug to treat SCD. Since 2017, three new drugs have been approved, but their costs and lack of long-term data have spawned questions regarding access and benefit.
“SCD reduces lifespan by 30 years, and that’s very hard to quantify,” says Ifeyinwa Osunkwo, MD, professor of medicine and pediatrics and director of Sickle Cell Disease Enterprise at the Levine Cancer Institute at Atrium Health in Charlotte, N.C. “If you put a dollar amount on what someone would make working for 30 adult years, that would be more reflective of the true cost of treating the disease.”
In 1984, hydroxyurea (Hydrea, Droxia) became the first drug to treat SCD in adults.
Originally developed as a myelosuppressive antineoplastic, hydroxyurea is used to treat resistant chronic myeloid leukemia and certain head and neck cancers. In SCD, it increases levels of hemoglobin and fetal hemoglobin.
Despite its benefit, hydroxyurea has two major drawbacks: It is only effective in two genotypes – HbSS or HbS/Beta0thal.
HbSS or HbS/Beta0thal genotypes account for 60% of the SCD population, but further studies are required to elucidate hydroxyurea’s effect in other forms of SCD, according to Dr. Osunkwo.
Secondly, hydroxyurea only reduces the frequency of painful episodes by 50% – not enough to ameliorate the pain, said John J. Strouse, MD, associate professor of medicine at Duke University School of Medicine.
Newer therapies offer the potential to enhance the effects of hydroxyurea when used concomitantly. They also give clinicians additional options for patients who either fail hydroxyurea therapy or for whom it is inappropriate.
The amino acid L-glutamine (Endari) became the second drug approved for sickle cell in 2017. Indicated for patients 5 years of age and older, Dr. Osunkwo says many patients were thrilled to have a nonchemotherapeutic option available. However, the medical community received the drug with some skepticism. “The data show Endari is moderately effective at best,” said Dr. Strouse. “Also, the mechanism of action is unclear.”
Additionally, the drug’s powder form and twice-daily dosing regimen make adherence more challenging than swallowing a few hydroxyurea tablets or capsules once a day. In Dr. Osunkwo’s experience, patients who respond best to Endari tend to be those who are naturally motivated individuals who are intentional in their efforts at optimizing their nutrition and self-care.
“It takes a lot to be adherent to Endari,” she said. “You have to work at it.”
On Nov. 15, 2019, the FDA approved crizanlizumab-tmca (Adakveo) for patients 16 years of age and older to decrease the occurrence of vasoocclusive crises.
The drug works by blocking selectin – a protein involved in the painful vascular pathophysiology. Patients receive a loading dose of 5 mg/kg administered via intravenous infusion over 30 minutes at the initiation of therapy, as well as weeks 2 and 4. After that, patients undergo treatment once a month. Nausea, back pain, pyrexia, and arthralgia are the most frequently reported adverse reactions. Clinicians must monitor patients for signs and symptoms of infusion-related reactions.
Ten days later, the FDA approved voxelotor (Oxbryta) for patients ages 12 years and up. The drug inhibits hemoglobin S polymerization and increases hemoglobin levels. Like hydroxyurea, the drug offers the convenience of once-daily dosing, and the tablet can be taken without regard to food. The drug dose requires adjustment for patients with severe hepatic impairment. Headache, fatigue, rash, and gastrointestinal disturbances such as diarrhea, nausea, and abdominal pain fall among the most commonly reported side effects.
Endari, Adakveo, and Oxbryta can all be used as monotherapy. They also provide additional benefits in reducing pain and hospitalizations and improving anemia when used concomitantly with hydroxyurea.
Like so many drugs, these novel therapies are expensive. The cost of these novel treatments has raised some eyebrows.
Annual costs of generic hydroxyurea range in the neighborhood of $1,200. In a 2017 CNBC interview, Endari manufacturer Emmaus stated that it aimed to keep drug costs under $20,000 a year. Annual costs for Adakveo and Oxbryta costs are in the neighborhood of $100,000. Adakveo manufacturer Novartis reportedly priced vials at $2,347. Most patients will require at least three of the maximum four vials per treatment. In a press release, Global Therapeutics stated that Oxbyta would cost $10,417 a month.
However, Dr. Osunkwo says the benefits of these new drugs far exceed the costs from both monetary and quality of life standpoints.
“Sickle cell disease is costly to manage,” she said in an interview. “One hospitalization can cost $10,000.”
Additionally, many SCD patients are publicly insured because of the profound disability and loss of productive work they encounter as a direct consequence of their disease and its complications. Those too sick to complete their high school and postsecondary education find limited employment opportunities.
Those fortunate enough to secure employment face significantly fewer years they can work because their pain, fatigue, frequent hospitalizations, and cumulative organ damage result in permanent disability. Only a smaller number of patients with less severe disease manifestations can secure steady employment and pursue careers that allow them to obtain private insurance.
Even if the newer therapies can help cut some costs, clinicians should be aware that prior authorizations can delay patient access to Adakveo and Oxbyta.
“We wrote the first prescription for Oxbryta in November of 2019, but the prior authorization wasn’t approved until February of 2020,” she said. Adding Adakveo to her institution’s formulary required several months of navigation. Given the arduous process, Dr. Osunkwo anticipates it will take at least year after approval before Adakveo is available for all eligible patients.
The long-term impact of these drugs also remains to be seen, so hydroxyurea will likely remain the drug of choice for many patients, according to Dr. Strouse.
Dr. Osunkwo believes SCD needs more drugs in order to truly optimize outcomes, contain costs, and enhance the patient experience.
Dr. Osunkwo reports consultancy and being on the speaker’s bureau and participating in the advisory board for Novartis, which markets Adakveo, and relationships with a variety of other pharmaceutical companies. She is the editor in chief for Hematology News. Dr. Strouse reports consultancy for Global Therapeutics, which markets Oxbryta.
Orthopedic ambulatory surgery centers beat inpatient services on cost
NATIONAL HARBOR, MD. – Hospital outpatient departments (HOPDs) and (IPs) with similar levels of postoperative opioid use, according to a new study.
Fanta Waterman, PhD, director of medical and health sciences at Pacira Pharmaceuticals, and colleagues retrospectively published the results of their investigation in the Journal of Managed Care & Specialty Pharmacy supplement for the annual meeting of the Academy of Managed Care Pharmacy.
Investigators evaluated data from 126,172 commercially insured patients who underwent one of six orthopedic surgical procedures between April 2012 and December 2017. Using the Optum Research Database, they pooled data from patients who had received total knee arthroplasty (TKA), partial knee arthroplasty, total hip arthroplasty (THA), rotator cuff repair (RCR), total shoulder arthroplasty, and lumbar spine fusion.
More than half (51%) of the patients were male, and the patients averaged 58 years of age. Most patients who underwent any of the six surgical interventions had the procedures performed at IPs (68%), while 18% had their operations at HOPDs and 14% were perfomed at ASCs.
TKA, RCR, and THA were the most common procedures performed (32%, 27%, and 20%, respectively). While no fluctuation was observed in the total number of IP procedures performed during 2012-2017, researchers noted a marked increase in ASCs (58%) and HOPDs (15%).
At the 30-day mark, the total all-cause postsurgical costs associated with IPs ($44,566) were more than double that of HOPDs ($20,468) and ASCs ($19,110; P less than .001). Moreover, multivariate adjustment showed that postsurgical costs accrued 30 days after surgery for HOPDs and ASCs were 14% and 27% lower than IPs (P less than .001), respectively.
Additionally, each group exhibited similar evidence of opioid use in the 12-month period prior to undergoing surgery, ranging from 63% to 65%. Postsurgical opioid use among opioid-naive patients was the highest in the HOPD group at 96% prevalence, with IPs and ASCs trailing with 91% and 90% (P less than .001), respectively. However, the postsurgical prevalence of opioid use in patients who had used opioids before surgery was 95% for IPs and HOPDs and 82% for ASCs (P less than .001).
SOURCE: Waterman F et al. AMCP NEXUS 2019, Abstract U12.
NATIONAL HARBOR, MD. – Hospital outpatient departments (HOPDs) and (IPs) with similar levels of postoperative opioid use, according to a new study.
Fanta Waterman, PhD, director of medical and health sciences at Pacira Pharmaceuticals, and colleagues retrospectively published the results of their investigation in the Journal of Managed Care & Specialty Pharmacy supplement for the annual meeting of the Academy of Managed Care Pharmacy.
Investigators evaluated data from 126,172 commercially insured patients who underwent one of six orthopedic surgical procedures between April 2012 and December 2017. Using the Optum Research Database, they pooled data from patients who had received total knee arthroplasty (TKA), partial knee arthroplasty, total hip arthroplasty (THA), rotator cuff repair (RCR), total shoulder arthroplasty, and lumbar spine fusion.
More than half (51%) of the patients were male, and the patients averaged 58 years of age. Most patients who underwent any of the six surgical interventions had the procedures performed at IPs (68%), while 18% had their operations at HOPDs and 14% were perfomed at ASCs.
TKA, RCR, and THA were the most common procedures performed (32%, 27%, and 20%, respectively). While no fluctuation was observed in the total number of IP procedures performed during 2012-2017, researchers noted a marked increase in ASCs (58%) and HOPDs (15%).
At the 30-day mark, the total all-cause postsurgical costs associated with IPs ($44,566) were more than double that of HOPDs ($20,468) and ASCs ($19,110; P less than .001). Moreover, multivariate adjustment showed that postsurgical costs accrued 30 days after surgery for HOPDs and ASCs were 14% and 27% lower than IPs (P less than .001), respectively.
Additionally, each group exhibited similar evidence of opioid use in the 12-month period prior to undergoing surgery, ranging from 63% to 65%. Postsurgical opioid use among opioid-naive patients was the highest in the HOPD group at 96% prevalence, with IPs and ASCs trailing with 91% and 90% (P less than .001), respectively. However, the postsurgical prevalence of opioid use in patients who had used opioids before surgery was 95% for IPs and HOPDs and 82% for ASCs (P less than .001).
SOURCE: Waterman F et al. AMCP NEXUS 2019, Abstract U12.
NATIONAL HARBOR, MD. – Hospital outpatient departments (HOPDs) and (IPs) with similar levels of postoperative opioid use, according to a new study.
Fanta Waterman, PhD, director of medical and health sciences at Pacira Pharmaceuticals, and colleagues retrospectively published the results of their investigation in the Journal of Managed Care & Specialty Pharmacy supplement for the annual meeting of the Academy of Managed Care Pharmacy.
Investigators evaluated data from 126,172 commercially insured patients who underwent one of six orthopedic surgical procedures between April 2012 and December 2017. Using the Optum Research Database, they pooled data from patients who had received total knee arthroplasty (TKA), partial knee arthroplasty, total hip arthroplasty (THA), rotator cuff repair (RCR), total shoulder arthroplasty, and lumbar spine fusion.
More than half (51%) of the patients were male, and the patients averaged 58 years of age. Most patients who underwent any of the six surgical interventions had the procedures performed at IPs (68%), while 18% had their operations at HOPDs and 14% were perfomed at ASCs.
TKA, RCR, and THA were the most common procedures performed (32%, 27%, and 20%, respectively). While no fluctuation was observed in the total number of IP procedures performed during 2012-2017, researchers noted a marked increase in ASCs (58%) and HOPDs (15%).
At the 30-day mark, the total all-cause postsurgical costs associated with IPs ($44,566) were more than double that of HOPDs ($20,468) and ASCs ($19,110; P less than .001). Moreover, multivariate adjustment showed that postsurgical costs accrued 30 days after surgery for HOPDs and ASCs were 14% and 27% lower than IPs (P less than .001), respectively.
Additionally, each group exhibited similar evidence of opioid use in the 12-month period prior to undergoing surgery, ranging from 63% to 65%. Postsurgical opioid use among opioid-naive patients was the highest in the HOPD group at 96% prevalence, with IPs and ASCs trailing with 91% and 90% (P less than .001), respectively. However, the postsurgical prevalence of opioid use in patients who had used opioids before surgery was 95% for IPs and HOPDs and 82% for ASCs (P less than .001).
SOURCE: Waterman F et al. AMCP NEXUS 2019, Abstract U12.
REPORTING FROM AMCP NEXUS 2019
Strategy critical to surviving drug shortages
NATIONAL HARBOR, MD. –
“Statistically speaking, there is no proof that patients are worse off from drug shortages,” Matt Grissinger, RPh, director of error-reporting programs at the Institute for Safe Medication Practices, told the audience at the annual conference of the Academy of Managed Care Pharmacy. The data and anecdotes he presented suggest the contrary.
As Mr. Grissinger pointed out, drug shortages can create a sequela of events that stress health care workers seeking to find the next-best available and most appropriate therapy for their patients. In the process, numerous medication-related errors can occur, resulting in patient harm, including adverse drug events and even death.
One potential problems is erroneous or inappropriate drug substitution stemming from mis- or uncalculated doses because of factors such as incorrect labeling and lack of knowledge regarding acceptable therapeutic interchanges. Other potential errors include non–therapeutically equivalent drug substitutions, resulting in supraoptimal therapy or overdoses, and unfamiliarity with drug labeling from outsourced facilities.
As a result, patients may experience worse outcomes as a consequence of the drug shortage: Worsening of the disease, disease prolongation, side effects stemming from alternative drug selections, untreated pain, psychological effects, severe electrolyte imbalances, severe acid/base imbalances, and death.
While a paper trail can help piece together clues regarding how a medication error occurred, documentation or lack thereof can also introduce errors when drug shortages occur.
Any changes to a drug order or prescription that deviate from the prescriber’s original request require prescriber approval but can still create opportunities for error. While documenting these changes and updating labeling is essential, appropriate documentation does not always occur and raises the question of who is responsible for making such changes.
Drug shortages also challenge a clinician’s professional judgment. Mr. Grissinger cited an example in which a nurse used half of a 0.5-mg single-use vial of promethazine for a patient requiring a 0.25 mg dose. The nurse wrote on the label that the remainder should be saved. While the vial was manufactured for one-time use, whether to discard the unused contents in a situation of drug shortages required the nurse to make a judgment call. In this case, the nurse chose to save the balance of the drug – a choice Mr. Grissinger stated he might have made had he been in a similar situation.
Additionally, drug shortages can create a climate in which more ethical questions arise – especially with regard to disease states such as cancer.
“If you only have 10 vials of vincristine, who gets it?” Mr. Grissinger asked the audience.
To help answer these difficult life-or-death questions, hospital settings need to engage the ethics committees and social workers.
While education plays a vital role in bringing attention to and addressing errors stemming from drug shortages, Mr. Grissinger cautioned the audience not to rely on education as the solution.
“Education is a poor strategy for addressing drug shortages,” he said. While education can draw awareness to drug shortages and subsequent medication-related errors, Mr. Grissinger recommends that organizations implement strategies to help ameliorate the havoc created by drug shortages.
Drug shortage assessment checklists can help organizations evaluate the impact of shortages by verifying inventory, and proactively searching for alternatives. From there, they can enact strategies such as assigning priority to patients who have the greatest need, altering packaging and concentrations, and finding suitable therapeutic substitutions.
NATIONAL HARBOR, MD. –
“Statistically speaking, there is no proof that patients are worse off from drug shortages,” Matt Grissinger, RPh, director of error-reporting programs at the Institute for Safe Medication Practices, told the audience at the annual conference of the Academy of Managed Care Pharmacy. The data and anecdotes he presented suggest the contrary.
As Mr. Grissinger pointed out, drug shortages can create a sequela of events that stress health care workers seeking to find the next-best available and most appropriate therapy for their patients. In the process, numerous medication-related errors can occur, resulting in patient harm, including adverse drug events and even death.
One potential problems is erroneous or inappropriate drug substitution stemming from mis- or uncalculated doses because of factors such as incorrect labeling and lack of knowledge regarding acceptable therapeutic interchanges. Other potential errors include non–therapeutically equivalent drug substitutions, resulting in supraoptimal therapy or overdoses, and unfamiliarity with drug labeling from outsourced facilities.
As a result, patients may experience worse outcomes as a consequence of the drug shortage: Worsening of the disease, disease prolongation, side effects stemming from alternative drug selections, untreated pain, psychological effects, severe electrolyte imbalances, severe acid/base imbalances, and death.
While a paper trail can help piece together clues regarding how a medication error occurred, documentation or lack thereof can also introduce errors when drug shortages occur.
Any changes to a drug order or prescription that deviate from the prescriber’s original request require prescriber approval but can still create opportunities for error. While documenting these changes and updating labeling is essential, appropriate documentation does not always occur and raises the question of who is responsible for making such changes.
Drug shortages also challenge a clinician’s professional judgment. Mr. Grissinger cited an example in which a nurse used half of a 0.5-mg single-use vial of promethazine for a patient requiring a 0.25 mg dose. The nurse wrote on the label that the remainder should be saved. While the vial was manufactured for one-time use, whether to discard the unused contents in a situation of drug shortages required the nurse to make a judgment call. In this case, the nurse chose to save the balance of the drug – a choice Mr. Grissinger stated he might have made had he been in a similar situation.
Additionally, drug shortages can create a climate in which more ethical questions arise – especially with regard to disease states such as cancer.
“If you only have 10 vials of vincristine, who gets it?” Mr. Grissinger asked the audience.
To help answer these difficult life-or-death questions, hospital settings need to engage the ethics committees and social workers.
While education plays a vital role in bringing attention to and addressing errors stemming from drug shortages, Mr. Grissinger cautioned the audience not to rely on education as the solution.
“Education is a poor strategy for addressing drug shortages,” he said. While education can draw awareness to drug shortages and subsequent medication-related errors, Mr. Grissinger recommends that organizations implement strategies to help ameliorate the havoc created by drug shortages.
Drug shortage assessment checklists can help organizations evaluate the impact of shortages by verifying inventory, and proactively searching for alternatives. From there, they can enact strategies such as assigning priority to patients who have the greatest need, altering packaging and concentrations, and finding suitable therapeutic substitutions.
NATIONAL HARBOR, MD. –
“Statistically speaking, there is no proof that patients are worse off from drug shortages,” Matt Grissinger, RPh, director of error-reporting programs at the Institute for Safe Medication Practices, told the audience at the annual conference of the Academy of Managed Care Pharmacy. The data and anecdotes he presented suggest the contrary.
As Mr. Grissinger pointed out, drug shortages can create a sequela of events that stress health care workers seeking to find the next-best available and most appropriate therapy for their patients. In the process, numerous medication-related errors can occur, resulting in patient harm, including adverse drug events and even death.
One potential problems is erroneous or inappropriate drug substitution stemming from mis- or uncalculated doses because of factors such as incorrect labeling and lack of knowledge regarding acceptable therapeutic interchanges. Other potential errors include non–therapeutically equivalent drug substitutions, resulting in supraoptimal therapy or overdoses, and unfamiliarity with drug labeling from outsourced facilities.
As a result, patients may experience worse outcomes as a consequence of the drug shortage: Worsening of the disease, disease prolongation, side effects stemming from alternative drug selections, untreated pain, psychological effects, severe electrolyte imbalances, severe acid/base imbalances, and death.
While a paper trail can help piece together clues regarding how a medication error occurred, documentation or lack thereof can also introduce errors when drug shortages occur.
Any changes to a drug order or prescription that deviate from the prescriber’s original request require prescriber approval but can still create opportunities for error. While documenting these changes and updating labeling is essential, appropriate documentation does not always occur and raises the question of who is responsible for making such changes.
Drug shortages also challenge a clinician’s professional judgment. Mr. Grissinger cited an example in which a nurse used half of a 0.5-mg single-use vial of promethazine for a patient requiring a 0.25 mg dose. The nurse wrote on the label that the remainder should be saved. While the vial was manufactured for one-time use, whether to discard the unused contents in a situation of drug shortages required the nurse to make a judgment call. In this case, the nurse chose to save the balance of the drug – a choice Mr. Grissinger stated he might have made had he been in a similar situation.
Additionally, drug shortages can create a climate in which more ethical questions arise – especially with regard to disease states such as cancer.
“If you only have 10 vials of vincristine, who gets it?” Mr. Grissinger asked the audience.
To help answer these difficult life-or-death questions, hospital settings need to engage the ethics committees and social workers.
While education plays a vital role in bringing attention to and addressing errors stemming from drug shortages, Mr. Grissinger cautioned the audience not to rely on education as the solution.
“Education is a poor strategy for addressing drug shortages,” he said. While education can draw awareness to drug shortages and subsequent medication-related errors, Mr. Grissinger recommends that organizations implement strategies to help ameliorate the havoc created by drug shortages.
Drug shortage assessment checklists can help organizations evaluate the impact of shortages by verifying inventory, and proactively searching for alternatives. From there, they can enact strategies such as assigning priority to patients who have the greatest need, altering packaging and concentrations, and finding suitable therapeutic substitutions.
REPORTING FROM AMCP NEXUS 2019
Technology softens prior authorization pain points
NATIONAL HARBOR, MD. – Nebulous pricing associated with prior authorization continues to be a major pain point for health care professionals, but this may become a thing of the past – thanks to a technology called real-time pharmacy benefit.
Real-time pharmacy benefits (RTPB) is software or a software component that allows practicing clinicians to look up a patient’s out-of-pocket costs for a specific drug, regardless of the patient’s health insurance coverage. Users can see the costs, copayment, and deductible for branded and generic, as well as compare insurance costs versus cash pricing.
Lindsey Colbert, RN, program manager for care team efficiency at HealthPartners, and Leann McDowell, PharmD, supervisor, pharmacy utilization management at HealthPartners, investigated how integrating RTPB software into their existing platforms and operations could help address pricing nuances and their associated burden on patients and health care professionals. They presented the results of their pilot test and post–pilot test expansion at the annual meeting of the Academy of Managed Care Pharmacy.
“Historically, clinicians were told not to quote prices, because having numerous insurance plans made it difficult to know what was going to be covered,” Ms. Colbert said. “Now, with real-time benefits, clinicians have pricing information readily available to them.”
HealthPartners pilot-tested RTPB at two locations before expanding to additional sites. They found that integrating real-time pharmacy benefits information improved the user experience and added cost savings for patients while improving workflow efficiency.
Health care professionals were more like to use RTPB for inquiries when the perceived patient cost was $50 or more – a price many clinicians perceive to be too expensive for many patients.
Before RTPB implementation, participating health care professionals reported waiting at least 45 minutes to get pricing on drugs requiring prior authorization. Integrating the RTPB software shaved the wait time down to 4 minutes – allowing them to quote drug prices to patients at the point of service.
Despite the benefits, everyone is not on board with RTPB.
Health care professionals already feel burdened by the information requirements of their electronic health records systems. They “count the number of computer clicks they have to make, so getting them to make an additional click to use RTPB requires another buy-in,” Ms. Colbert said.
While participating health care professionals were asked to run every prescription through RTPB, they reported using the software only when they knew a patient would either perceive cost as a potential barrier, or if they knew a drug would be expensive.
Investigators said they plan to continue working with clinicians to make RTPB integration more user-friendly by eventually eliminating the additional computer click required to run the program. They also plan to monitor the progress of the National Council for Prescription Drug Programs – developer of RTPB – regarding its adaptation of its new standard.
NATIONAL HARBOR, MD. – Nebulous pricing associated with prior authorization continues to be a major pain point for health care professionals, but this may become a thing of the past – thanks to a technology called real-time pharmacy benefit.
Real-time pharmacy benefits (RTPB) is software or a software component that allows practicing clinicians to look up a patient’s out-of-pocket costs for a specific drug, regardless of the patient’s health insurance coverage. Users can see the costs, copayment, and deductible for branded and generic, as well as compare insurance costs versus cash pricing.
Lindsey Colbert, RN, program manager for care team efficiency at HealthPartners, and Leann McDowell, PharmD, supervisor, pharmacy utilization management at HealthPartners, investigated how integrating RTPB software into their existing platforms and operations could help address pricing nuances and their associated burden on patients and health care professionals. They presented the results of their pilot test and post–pilot test expansion at the annual meeting of the Academy of Managed Care Pharmacy.
“Historically, clinicians were told not to quote prices, because having numerous insurance plans made it difficult to know what was going to be covered,” Ms. Colbert said. “Now, with real-time benefits, clinicians have pricing information readily available to them.”
HealthPartners pilot-tested RTPB at two locations before expanding to additional sites. They found that integrating real-time pharmacy benefits information improved the user experience and added cost savings for patients while improving workflow efficiency.
Health care professionals were more like to use RTPB for inquiries when the perceived patient cost was $50 or more – a price many clinicians perceive to be too expensive for many patients.
Before RTPB implementation, participating health care professionals reported waiting at least 45 minutes to get pricing on drugs requiring prior authorization. Integrating the RTPB software shaved the wait time down to 4 minutes – allowing them to quote drug prices to patients at the point of service.
Despite the benefits, everyone is not on board with RTPB.
Health care professionals already feel burdened by the information requirements of their electronic health records systems. They “count the number of computer clicks they have to make, so getting them to make an additional click to use RTPB requires another buy-in,” Ms. Colbert said.
While participating health care professionals were asked to run every prescription through RTPB, they reported using the software only when they knew a patient would either perceive cost as a potential barrier, or if they knew a drug would be expensive.
Investigators said they plan to continue working with clinicians to make RTPB integration more user-friendly by eventually eliminating the additional computer click required to run the program. They also plan to monitor the progress of the National Council for Prescription Drug Programs – developer of RTPB – regarding its adaptation of its new standard.
NATIONAL HARBOR, MD. – Nebulous pricing associated with prior authorization continues to be a major pain point for health care professionals, but this may become a thing of the past – thanks to a technology called real-time pharmacy benefit.
Real-time pharmacy benefits (RTPB) is software or a software component that allows practicing clinicians to look up a patient’s out-of-pocket costs for a specific drug, regardless of the patient’s health insurance coverage. Users can see the costs, copayment, and deductible for branded and generic, as well as compare insurance costs versus cash pricing.
Lindsey Colbert, RN, program manager for care team efficiency at HealthPartners, and Leann McDowell, PharmD, supervisor, pharmacy utilization management at HealthPartners, investigated how integrating RTPB software into their existing platforms and operations could help address pricing nuances and their associated burden on patients and health care professionals. They presented the results of their pilot test and post–pilot test expansion at the annual meeting of the Academy of Managed Care Pharmacy.
“Historically, clinicians were told not to quote prices, because having numerous insurance plans made it difficult to know what was going to be covered,” Ms. Colbert said. “Now, with real-time benefits, clinicians have pricing information readily available to them.”
HealthPartners pilot-tested RTPB at two locations before expanding to additional sites. They found that integrating real-time pharmacy benefits information improved the user experience and added cost savings for patients while improving workflow efficiency.
Health care professionals were more like to use RTPB for inquiries when the perceived patient cost was $50 or more – a price many clinicians perceive to be too expensive for many patients.
Before RTPB implementation, participating health care professionals reported waiting at least 45 minutes to get pricing on drugs requiring prior authorization. Integrating the RTPB software shaved the wait time down to 4 minutes – allowing them to quote drug prices to patients at the point of service.
Despite the benefits, everyone is not on board with RTPB.
Health care professionals already feel burdened by the information requirements of their electronic health records systems. They “count the number of computer clicks they have to make, so getting them to make an additional click to use RTPB requires another buy-in,” Ms. Colbert said.
While participating health care professionals were asked to run every prescription through RTPB, they reported using the software only when they knew a patient would either perceive cost as a potential barrier, or if they knew a drug would be expensive.
Investigators said they plan to continue working with clinicians to make RTPB integration more user-friendly by eventually eliminating the additional computer click required to run the program. They also plan to monitor the progress of the National Council for Prescription Drug Programs – developer of RTPB – regarding its adaptation of its new standard.
REPORTING FROM AMCP NEXUS 2019