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Prodromal Parkinson’s disease tied to significant functional impairment
new research shows.
The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.
“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”
The findings were published online in JAMA Neurology.
Improving quality of life
Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold.
To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.
Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.
Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.
“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
Serving patients better
Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.
This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote .
“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.
One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.
“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”
The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.
A version of this article first appeared on Medscape.com.
new research shows.
The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.
“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”
The findings were published online in JAMA Neurology.
Improving quality of life
Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold.
To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.
Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.
Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.
“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
Serving patients better
Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.
This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote .
“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.
One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.
“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”
The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.
A version of this article first appeared on Medscape.com.
new research shows.
The new findings come from a large case-control study that analyzed Medicare claims data to evaluate functional limitations in prodromal Parkinson’s disease, leading the investigators to suggest prodromal Parkinson’s disease should be recognized as a distinct disease stage.
“It’s increasingly recognized as a stage of Parkinson’s and there is an argument here for that,” said lead investigator Cameron Miller-Patterson, MD, assistant professor of neurology at Virginia Commonwealth University, Richmond. “Because we’re finding that people with prodromal Parkinson’s disease may have functional limitations, identifying them sooner and getting them the appropriate symptomatic therapy could be helpful.”
The findings were published online in JAMA Neurology.
Improving quality of life
Individuals with prodromal Parkinson’s disease have symptoms of Parkinson’s disease, but not enough to meet diagnostic criteria. However, all patients with prodromal Parkinson’s disease eventually meet that threshold.
To evaluate whether functional limitations are present in individuals with Parkinson’s disease prior to diagnosis versus the general population, researchers analyzed Medicare-linked data on 6,674 individuals aged 65 years and older who participated in the National Health and Aging Trends Study, a longitudinal survey in the United States. Survey questions evaluated dexterity, eating, mobility, mood, pain, sleep, speech, strength, and vision.
Patients with incident Parkinson’s disease were defined as having two or more Medicare diagnoses. Controls were defined as those with Medicare eligibility at baseline and 2 or more years prior, with no diagnosis.
Compared with individuals who never had Parkinson’s disease, those who eventually received a diagnosis were less likely to report being able to walk 6 blocks (odds ratio, 0.34; 95% confidence interval, 0.15-0.82), stand independently from kneeling (OR, 0.30; 95% CI, 0.11-0.85) or lift a heavy object overhead (OR, 0.36; 95% CI, 0.15-0.87). They were also more likely to report imbalance (OR, 2.77; 95% CI, 1.24-6.20) 3 years prior to diagnosis.
“Generally, we don’t start treating people until we see them in the clinic and give them a diagnosis of Parkinson’s disease,” Dr. Miller-Patterson said. “If we identify them earlier, even before diagnosis, we may be able to improve their quality of life by treating them sooner.”
Serving patients better
Better recognition of prodromal Parkinson’s disease could also help identify participants for clinical trials of therapeutics that could slow disease progression, something that is beyond the ability of currently approved medications.
This, and growing support for distinguishing prodromal Parkinson’s disease as an official stage of Parkinson’s disease, makes findings such as these both timely and important, the authors of an accompanying commentary wrote .
“The recognition of a prodromal period has been viewed as potentially critical to the success of disease-modifying interventions, on the argument that it may be too late to enact meaningful clinical change once symptoms clinically manifest given the degree of neurodegeneration already present,” Ian O. Bledsoe, MD, Weill Institute for Neurosciences, University of California, San Francisco, and coauthors wrote.
One limitation, however, is that the study design didn’t allow researchers to determine if individuals with eventual Parkinson’s disease who reported parkinsonian symptoms had prodromal Parkinson’s disease or undiagnosed disease. The answer would clarify whether prodromal Parkinson’s disease is more common than previously thought or if Parkinson’s disease diagnosis is often delayed for years – or both.
“Despite the limitations of this study, its broader point and importance remain: People appear to have some markers of functional decline before they are diagnosed with Parkinson’s disease,” the editorialists wrote. “Additionally, motor dysfunction may arise at an earlier time point in the disease than we typically think. There is a potential opportunity to serve this population better.”
The study was funded by the National Institutes of Health. Dr. Miller-Patterson reported receiving other NIH grants during the course of the study. Dr. Bledsoe reported personal fees from Boston Scientific, Amneal Pharmaceuticals, IDEO, Accorda, Humancraft.com, and Putnam Associates, as well as grants from the National Institutes of Health, the Michael J. Fox Foundation, and Dystonia Medical.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Cluster headache tied to high risk of mental and neurologic disorders
, leading to significant disability and absenteeism, new research shows.
Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.
Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.
“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.
“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.
The findings were published online in Neurology.
‘Striking’ finding
Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.
Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.
The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.
Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).
Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).
The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.
Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.
“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
Risky behavior?
Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.
In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.
“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.
Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).
Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).
Removing mental and behavioral health disorders from the mix did not lower those numbers.
“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
Struggle is real
Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.
“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.
“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.
Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.
“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”
The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.
“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.
The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, leading to significant disability and absenteeism, new research shows.
Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.
Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.
“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.
“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.
The findings were published online in Neurology.
‘Striking’ finding
Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.
Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.
The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.
Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).
Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).
The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.
Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.
“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
Risky behavior?
Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.
In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.
“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.
Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).
Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).
Removing mental and behavioral health disorders from the mix did not lower those numbers.
“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
Struggle is real
Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.
“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.
“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.
Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.
“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”
The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.
“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.
The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, leading to significant disability and absenteeism, new research shows.
Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.
Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.
“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.
“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.
The findings were published online in Neurology.
‘Striking’ finding
Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.
Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.
The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.
Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).
Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).
The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.
Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.
“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
Risky behavior?
Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.
In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.
“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.
Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).
Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).
Removing mental and behavioral health disorders from the mix did not lower those numbers.
“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
Struggle is real
Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.
“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.
“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.
Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.
“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”
The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.
“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.
The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Annual U.S. Parkinson’s disease incidence 50% higher than earlier estimates
according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.
In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.
This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.
“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.
“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.
The findings were published online in NPJ Parkinson’s Disease.
Updating an outdated model
The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.
Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.
Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.
The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).
On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.
That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.
“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”
Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”
That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.
Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
Why the increase?
The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.
“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.
Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.
“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.
That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.
The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.
In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.
“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.
“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
‘Groundbreaking’ findings
Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.
“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.
She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.
“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.
This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.
“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.
The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.
In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.
This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.
“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.
“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.
The findings were published online in NPJ Parkinson’s Disease.
Updating an outdated model
The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.
Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.
Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.
The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).
On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.
That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.
“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”
Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”
That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.
Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
Why the increase?
The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.
“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.
Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.
“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.
That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.
The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.
In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.
“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.
“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
‘Groundbreaking’ findings
Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.
“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.
She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.
“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.
This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.
“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.
The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new research that investigators say highlights the growing strain on clinical services and the need for more research funding.
In an analysis of five databases and more than 15 million people, about 60,000-90,000 individuals older than 45 years are estimated to be diagnosed with Parkinson’s disease each year – which is far more than the previous estimate of around 40,000-60,000 new cases annually.
This is the latest study to update decades-old epidemiologic data on Parkinson’s disease incidence and prevalence. Previous incidence rates came from small, single-population studies that are now more than 25 years old.
“In the advocacy community, we’ve been earnest about the impact of people living with Parkinson’s disease, and what we really lacked was sufficient data to be able to demonstrate the urgency of our need,” said study coinvestigator James Beck, PhD, chief scientific officer at the Parkinson’s Foundation, New York.
“We wanted to revise these numbers, highlight that they are larger than people anticipated, and use it as a call to action to change the approach we have toward Parkinson’s,” Dr. Beck said.
The findings were published online in NPJ Parkinson’s Disease.
Updating an outdated model
The study builds on the Parkinson’s Prevalence Project, a 2018 initiative that used a new model to calculate Parkinson’s disease prevalence. Before then, federal prevalence data was based on a 40-year-old study of just 26 Parkinson’s disease cases in one small county in rural Mississippi.
Dr. Beck and others used a more sophisticated model, using data from five separate cohort studies. They estimated the total number of patients living with Parkinson’s disease in the United States to be 930,000, which is far higher than the 650,000 the old model predicted.
Researchers then moved on to the current project, developing a new method to estimate Parkinson’s disease incidence.
The project included 2012 data on more than 15 million individuals in the United States and Canada. The investigators drew from three large insurance databases (Kaiser Permanente Northern California, Ontario Health Care, and Medicare) and two long-term epidemiologic studies (the Honolulu-Asia Aging Study and the Rochester Epidemiology Project).
On the basis of their analysis, the investigators proposed a working Parkinson’s disease incident rate estimate of 47-77 cases per 100,000 people aged 45 years or older. Limiting the analysis to those aged 65 or older raised the incidence to 108-212 per 100,000 people.
That translates to 60,000-95,000 new cases each year among adults aged 45 years or older. Using the Medicare administrative database alone for this same time period suggests an annual incidence of nearly 90,000 for individuals aged 65 or older.
“The numbers we’re proposing are conservative,” Dr. Beck said. “The true numbers are probably north of 90,000.”
Incidence rates increased with age and were higher in men. The researchers also identified clusters of counties with higher incidence rates in parts of the country called the “Parkinson’s belt.”
That geographic area mirrors the Rust Belt and includes parts of the Northeastern and Midwestern United States with a long history of industrial manufacturing that used heavy metals and industrial solvents, which are environmental factors linked to risk for Parkinson’s disease.
Cases were also higher in southern California, southeastern Texas, and Florida – agricultural regions with high pesticide use, which is also a risk factor for Parkinson’s disease. Central Pennsylvania also had higher incidence rates.
Why the increase?
The increase in cases could be the result of the more comprehensive estimation model used, the researchers noted. Or it could be improved detection, the aging population, a rise in sedentary lifestyles, increased exposure to environmental risk factors, or even the sharp decline in smoking in the United States, as some studies have shown that smokers have a lower Parkinson’s disease risk.
“The short answer is, we don’t know; and the long answer is, it’s all the above,” Dr. Beck said.
Although about 15% of Parkinson’s disease cases have a genetic basis, the cause is unknown in the majority of cases. In addition, diagnosis is difficult because there is no blood test or scan that detects the disease.
“Diagnosis requires a skilled clinician with real familiarity with Parkinson’s. And we have a real shortage of neurologists in this country to not only be able to diagnose but also to treat the condition,” Dr. Beck said.
That was one motivation for doing the study: to highlight what experts say is a pending clinical crisis for patients with Parkinson’s disease, he added.
The investigators also wanted to raise awareness about the scope of the disorder – not just about prevalence and incidence but also what those data mean for the health care industry, research aims, drug development and health care coverage, and policies.
In a 2020 study, the same researchers calculated a cost of $52 billion per year for medical and nonmedical costs related to Parkinson’s disease, which works out to about $26,000 per year per patient. That figure is expected to surpass $79 billion by 2030.
“This is an urgent condition for many people who live with the disease. And to the extent we can get our country to recognize that and really make the investment now, this is an area where a stitch in time saves nine,” Dr. Beck said.
“If we can invest some money now, we have a chance to really make a difference in the future,” he added.
‘Groundbreaking’ findings
Commenting on the findings, Jori Fleisher, MD, MSCE, associate professor of neurological sciences at Rush University Medical Center, Chicago, called the results “groundbreaking” and said that they validate what clinicians have been seeing in real-world practice.
“The findings reflect what a lot of us in practice have been appreciating anecdotally, which is that it seems that Parkinson’s is being diagnosed more frequently and that the incidence has been rising,” said Dr. Fleisher, who was not involved with the study.
She noted that the use of multiple datasets is one element of the methodology that makes the data so significant.
“There has been great work out of individual centers; but no matter how good your study methods are within that one population, you’re drawing conclusions based on that one population,” Dr. Fleisher said.
This research, together with the previous work by the group on prevalence data, could go a long way toward raising awareness about the scope of Parkinson’s disease in the United States – which could lead to earlier diagnosis, more research funding, and increased attention on the need for more clinicians who specialize in movement disorders, she added.
“This should increase research funding across the spectrum, including everything from the basic science to translational research, clinical research and implementation, and health services research,” Dr. Fleisher said.
The study was supported by the Parkinson’s Foundation, The Michael J. Fox Foundation for Parkinson’s Research, and the Institute for Clinical Evaluative Sciences. Dr. Beck and Dr. Fleisher reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NPJ PARKINSON’S DISEASE
New framework for MS diagnosis and treatment proposed
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Traffic-related pollutant tied to increased dementia risk
Exposure to a traffic-related air pollutant significantly increases risk for dementia, new research suggests. Results from a meta-analysis, which included a total of more than 90 million people, showed
Particulate matter is a mixture of solid particles and liquid droplets from the burning of fossil fuels and nitrogen oxide, and also produced from road traffic exhaust.
While the research only showed an association between this type of air pollution and dementia risk, the estimates were consistent across the different analyses used.
“It’s rather sobering that there is this 3% relationship between incidence of dementia and the particulate matter and that it is such a precise estimate,” senior investigator Janet Martin, PharmD, MSc, associate professor of anesthesia & perioperative medicine and epidemiology & biostatistics at Western University’s, London, Ont., told this news organization.
The findings were published online in Neurology.
Conflicting results in past studies
Air pollution is a known risk factor for dementia, but studies attempting to pinpoint its exact impact have yielded conflicting results.
Researchers analyzed data from 17 studies with a total of 91.4 million individuals, 6% of whom had dementia. In addition to PM2.5, the investigators also assessed nitrogen oxides, which form smog, nitrogen dioxide, and ozone exposure.
After adjustments for other known risk factors, such as age and gender, results showed that dementia risk increased by 3% for every 1 m3 rise in PM2.5 exposure (adjusted hazard ratio, 1.03; 95% confidence interval, 1.02-1.05).
The associations between dementia and exposure to nitrogen oxides (HR, 1.05; 95% CI, 0.99-1.13), nitrogen dioxide (HR, 1.03; 95% CI, 1.00-1.07) and ozone (HR, 1.01; 95% CI, 0.91-1.11) did not reach statistical significance. However, the confidence intervals were wide enough that clinical relevance cannot be ruled out, Dr. Martin said.
The study did not examine how or if the duration of PM2.5 exposure affected dementia risk. In addition, the investigators were not able to identify a threshold above which dementia risk begins to rise.
The Environmental Pollution Agency considers average yearly exposures up to 12 mcg/m3 to be safe. The World Health Organization sets that limit lower, at 5 mcg/m3.
Dr. Martin noted that more studies are needed to explore those issues, as well as the mechanisms by which air pollutants contribute to the pathology of dementia. However, the clear link between fine particulate matter exposure and increased risk emphasizes the need to address air pollution as a modifiable risk factor for dementia.
“The rising tide of dementia is not something we can easily reverse,” Dr. Martin said. “The evidence has been so elusive for how to treat dementia once you have it, so our biggest opportunity is to prevent it.”
Results from a study published earlier in 2022 estimated that rates of dementia will triple worldwide and double in the United States by 2050 unless steps are taking to mitigate risk factors.
Research also suggests that improving air quality PM2.5 by just 10% results in a 14% decreased risk for dementia.
‘Impressive’ pattern
Paul Rosenberg, MD, codirector of the Memory and Alzheimer’s Treatment Center division of geriatric psychiatry at Johns Hopkins University, Baltimore, said that air pollution “is the most prominent environmental risk we’ve found” for dementia. It also “adds to many other lifestyle and comorbidity risks, such as lack of exercise, obesity, depression, hearing loss, etc,” said Dr. Rosenberg, who was not involved with the research.
He noted what was “most impressive” was that in most of the pooled studies, small particulate air pollution was associated with dementia. “The overall pattern is most impressive and the effect sizes quite consistent over most of the studies,” Dr. Rosenberg said.
The meta-analysis was unfunded. Dr. Martin and Dr. Rosenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to a traffic-related air pollutant significantly increases risk for dementia, new research suggests. Results from a meta-analysis, which included a total of more than 90 million people, showed
Particulate matter is a mixture of solid particles and liquid droplets from the burning of fossil fuels and nitrogen oxide, and also produced from road traffic exhaust.
While the research only showed an association between this type of air pollution and dementia risk, the estimates were consistent across the different analyses used.
“It’s rather sobering that there is this 3% relationship between incidence of dementia and the particulate matter and that it is such a precise estimate,” senior investigator Janet Martin, PharmD, MSc, associate professor of anesthesia & perioperative medicine and epidemiology & biostatistics at Western University’s, London, Ont., told this news organization.
The findings were published online in Neurology.
Conflicting results in past studies
Air pollution is a known risk factor for dementia, but studies attempting to pinpoint its exact impact have yielded conflicting results.
Researchers analyzed data from 17 studies with a total of 91.4 million individuals, 6% of whom had dementia. In addition to PM2.5, the investigators also assessed nitrogen oxides, which form smog, nitrogen dioxide, and ozone exposure.
After adjustments for other known risk factors, such as age and gender, results showed that dementia risk increased by 3% for every 1 m3 rise in PM2.5 exposure (adjusted hazard ratio, 1.03; 95% confidence interval, 1.02-1.05).
The associations between dementia and exposure to nitrogen oxides (HR, 1.05; 95% CI, 0.99-1.13), nitrogen dioxide (HR, 1.03; 95% CI, 1.00-1.07) and ozone (HR, 1.01; 95% CI, 0.91-1.11) did not reach statistical significance. However, the confidence intervals were wide enough that clinical relevance cannot be ruled out, Dr. Martin said.
The study did not examine how or if the duration of PM2.5 exposure affected dementia risk. In addition, the investigators were not able to identify a threshold above which dementia risk begins to rise.
The Environmental Pollution Agency considers average yearly exposures up to 12 mcg/m3 to be safe. The World Health Organization sets that limit lower, at 5 mcg/m3.
Dr. Martin noted that more studies are needed to explore those issues, as well as the mechanisms by which air pollutants contribute to the pathology of dementia. However, the clear link between fine particulate matter exposure and increased risk emphasizes the need to address air pollution as a modifiable risk factor for dementia.
“The rising tide of dementia is not something we can easily reverse,” Dr. Martin said. “The evidence has been so elusive for how to treat dementia once you have it, so our biggest opportunity is to prevent it.”
Results from a study published earlier in 2022 estimated that rates of dementia will triple worldwide and double in the United States by 2050 unless steps are taking to mitigate risk factors.
Research also suggests that improving air quality PM2.5 by just 10% results in a 14% decreased risk for dementia.
‘Impressive’ pattern
Paul Rosenberg, MD, codirector of the Memory and Alzheimer’s Treatment Center division of geriatric psychiatry at Johns Hopkins University, Baltimore, said that air pollution “is the most prominent environmental risk we’ve found” for dementia. It also “adds to many other lifestyle and comorbidity risks, such as lack of exercise, obesity, depression, hearing loss, etc,” said Dr. Rosenberg, who was not involved with the research.
He noted what was “most impressive” was that in most of the pooled studies, small particulate air pollution was associated with dementia. “The overall pattern is most impressive and the effect sizes quite consistent over most of the studies,” Dr. Rosenberg said.
The meta-analysis was unfunded. Dr. Martin and Dr. Rosenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to a traffic-related air pollutant significantly increases risk for dementia, new research suggests. Results from a meta-analysis, which included a total of more than 90 million people, showed
Particulate matter is a mixture of solid particles and liquid droplets from the burning of fossil fuels and nitrogen oxide, and also produced from road traffic exhaust.
While the research only showed an association between this type of air pollution and dementia risk, the estimates were consistent across the different analyses used.
“It’s rather sobering that there is this 3% relationship between incidence of dementia and the particulate matter and that it is such a precise estimate,” senior investigator Janet Martin, PharmD, MSc, associate professor of anesthesia & perioperative medicine and epidemiology & biostatistics at Western University’s, London, Ont., told this news organization.
The findings were published online in Neurology.
Conflicting results in past studies
Air pollution is a known risk factor for dementia, but studies attempting to pinpoint its exact impact have yielded conflicting results.
Researchers analyzed data from 17 studies with a total of 91.4 million individuals, 6% of whom had dementia. In addition to PM2.5, the investigators also assessed nitrogen oxides, which form smog, nitrogen dioxide, and ozone exposure.
After adjustments for other known risk factors, such as age and gender, results showed that dementia risk increased by 3% for every 1 m3 rise in PM2.5 exposure (adjusted hazard ratio, 1.03; 95% confidence interval, 1.02-1.05).
The associations between dementia and exposure to nitrogen oxides (HR, 1.05; 95% CI, 0.99-1.13), nitrogen dioxide (HR, 1.03; 95% CI, 1.00-1.07) and ozone (HR, 1.01; 95% CI, 0.91-1.11) did not reach statistical significance. However, the confidence intervals were wide enough that clinical relevance cannot be ruled out, Dr. Martin said.
The study did not examine how or if the duration of PM2.5 exposure affected dementia risk. In addition, the investigators were not able to identify a threshold above which dementia risk begins to rise.
The Environmental Pollution Agency considers average yearly exposures up to 12 mcg/m3 to be safe. The World Health Organization sets that limit lower, at 5 mcg/m3.
Dr. Martin noted that more studies are needed to explore those issues, as well as the mechanisms by which air pollutants contribute to the pathology of dementia. However, the clear link between fine particulate matter exposure and increased risk emphasizes the need to address air pollution as a modifiable risk factor for dementia.
“The rising tide of dementia is not something we can easily reverse,” Dr. Martin said. “The evidence has been so elusive for how to treat dementia once you have it, so our biggest opportunity is to prevent it.”
Results from a study published earlier in 2022 estimated that rates of dementia will triple worldwide and double in the United States by 2050 unless steps are taking to mitigate risk factors.
Research also suggests that improving air quality PM2.5 by just 10% results in a 14% decreased risk for dementia.
‘Impressive’ pattern
Paul Rosenberg, MD, codirector of the Memory and Alzheimer’s Treatment Center division of geriatric psychiatry at Johns Hopkins University, Baltimore, said that air pollution “is the most prominent environmental risk we’ve found” for dementia. It also “adds to many other lifestyle and comorbidity risks, such as lack of exercise, obesity, depression, hearing loss, etc,” said Dr. Rosenberg, who was not involved with the research.
He noted what was “most impressive” was that in most of the pooled studies, small particulate air pollution was associated with dementia. “The overall pattern is most impressive and the effect sizes quite consistent over most of the studies,” Dr. Rosenberg said.
The meta-analysis was unfunded. Dr. Martin and Dr. Rosenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Can MS be stopped early in its tracks?
, the earliest detected preclinical phase of multiple sclerosis (MS). Researchers found that dimethyl fumarate reduced the risk of a first acute or progressive event related to CNS demyelination by more than 80%, compared with placebo.
Patients with RIS have incidental MRI abnormalities typical of MS but have no symptoms of the disease. The condition is usually detected when a patient seeks treatment for another issue, such as migraines or head trauma.
The study is the first randomized clinical trial to examine efficacy of a disease-modifying therapy in delaying symptoms in RIS. “It really supports the concept of the benefit of early treatment intervention within this given MS disease spectrum,” lead investigator Darin Okuda, MD, professor of neurology at the University of Texas Southwestern Medical Center in Dallas, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
Topic of debate
RIS was first identified by Dr. Okuda in 2008. Increased use of brain imaging led to the detection of patients with incidental white-matter pathology in the central nervous system on MRI. Some of the findings were nonspecific, but others were highly suggestive of demyelinating pathology based on their location and morphology in the central nervous system.
Although the prevalence of RIS is unknown, incidentally discovered white matter lesions resembling demyelination occur in an estimated 0.1%-0.7% of the general population. Up to half of patients with RIS experience a first clinical MS event within 10 years.
Diagnostic criteria and whether to treat patients with RIS prophylactically has long been a topic of debate among neurologists and radiologists.
Researchers conducted the multicenter, randomized, double-blinded, placebo-controlled ARISE study in 2016, recruiting 87 patients with RIS. The majority of participants were women, and most were diagnosed in their early 40s.
Patients received oral dimethyl fumarate at 240 mg twice daily or placebo and were followed for 96 weeks (1 year, 10 months). Clinical assessments were completed at baseline, at weeks 48 and 96, and at the time of the first clinical event. MRI scans were performed only at the beginning and end of the study.
Those who received dimethyl fumarate had a significantly lower risk of experiencing a first clinical demyelinating event during the study period (adjusted hazard ratio, 0.07; P = .005).
After adjusting for the number of gadolinium-enhancing lesions at baseline, there was a significant reduction in the number of new or newly enlarged T2-weighted hyperintense lesions, a secondary endpoint, in the dimethyl fumarate group, compared with those on placebo (HR, 0.20; P = .042).
“In the future we’d like to see further studies performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time,” Dr. Okuda said.
‘Striking’ findings
Barbara Giesser, MD, a neurologist at Pacific Neuroscience Institute in Santa Monica, Calif., called the results “striking,” but noted that questions remain.
“Up until this study we haven’t had anything like it to guide us in determining whether we should treat RIS or not,” she said. “Obviously, larger studies are needed, but I think this is a very important and well-done study.”
In addition to the small sample size, Dr. Giesser noted that the study lacked data on the presence of risk factors that are known to increase RIS patients’ risk of developing MS, such as evidence of spinal cord lesions. That issue was also raised during discussion of the paper in Amsterdam.
“I don’t think this means you should treat everybody with RIS necessarily,” Dr. Giesser said. “But I think it suggests that in people with RIS, particularly if they do have risk factors, you could consider treatment with dimethyl fumarate.”
The study was funded by Biogen. Dr. Okuda has received support from Biogen and EMD Serono/Merck; and consulting fees from Alexion, Biogen, EMD Serono, Genzyme, Novartis, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, Celgene/Bristol Myers Squibb, Genentech, Janssen Pharmaceuticals, and Osmotica Pharmaceuticals. Dr. Giesser reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, the earliest detected preclinical phase of multiple sclerosis (MS). Researchers found that dimethyl fumarate reduced the risk of a first acute or progressive event related to CNS demyelination by more than 80%, compared with placebo.
Patients with RIS have incidental MRI abnormalities typical of MS but have no symptoms of the disease. The condition is usually detected when a patient seeks treatment for another issue, such as migraines or head trauma.
The study is the first randomized clinical trial to examine efficacy of a disease-modifying therapy in delaying symptoms in RIS. “It really supports the concept of the benefit of early treatment intervention within this given MS disease spectrum,” lead investigator Darin Okuda, MD, professor of neurology at the University of Texas Southwestern Medical Center in Dallas, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
Topic of debate
RIS was first identified by Dr. Okuda in 2008. Increased use of brain imaging led to the detection of patients with incidental white-matter pathology in the central nervous system on MRI. Some of the findings were nonspecific, but others were highly suggestive of demyelinating pathology based on their location and morphology in the central nervous system.
Although the prevalence of RIS is unknown, incidentally discovered white matter lesions resembling demyelination occur in an estimated 0.1%-0.7% of the general population. Up to half of patients with RIS experience a first clinical MS event within 10 years.
Diagnostic criteria and whether to treat patients with RIS prophylactically has long been a topic of debate among neurologists and radiologists.
Researchers conducted the multicenter, randomized, double-blinded, placebo-controlled ARISE study in 2016, recruiting 87 patients with RIS. The majority of participants were women, and most were diagnosed in their early 40s.
Patients received oral dimethyl fumarate at 240 mg twice daily or placebo and were followed for 96 weeks (1 year, 10 months). Clinical assessments were completed at baseline, at weeks 48 and 96, and at the time of the first clinical event. MRI scans were performed only at the beginning and end of the study.
Those who received dimethyl fumarate had a significantly lower risk of experiencing a first clinical demyelinating event during the study period (adjusted hazard ratio, 0.07; P = .005).
After adjusting for the number of gadolinium-enhancing lesions at baseline, there was a significant reduction in the number of new or newly enlarged T2-weighted hyperintense lesions, a secondary endpoint, in the dimethyl fumarate group, compared with those on placebo (HR, 0.20; P = .042).
“In the future we’d like to see further studies performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time,” Dr. Okuda said.
‘Striking’ findings
Barbara Giesser, MD, a neurologist at Pacific Neuroscience Institute in Santa Monica, Calif., called the results “striking,” but noted that questions remain.
“Up until this study we haven’t had anything like it to guide us in determining whether we should treat RIS or not,” she said. “Obviously, larger studies are needed, but I think this is a very important and well-done study.”
In addition to the small sample size, Dr. Giesser noted that the study lacked data on the presence of risk factors that are known to increase RIS patients’ risk of developing MS, such as evidence of spinal cord lesions. That issue was also raised during discussion of the paper in Amsterdam.
“I don’t think this means you should treat everybody with RIS necessarily,” Dr. Giesser said. “But I think it suggests that in people with RIS, particularly if they do have risk factors, you could consider treatment with dimethyl fumarate.”
The study was funded by Biogen. Dr. Okuda has received support from Biogen and EMD Serono/Merck; and consulting fees from Alexion, Biogen, EMD Serono, Genzyme, Novartis, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, Celgene/Bristol Myers Squibb, Genentech, Janssen Pharmaceuticals, and Osmotica Pharmaceuticals. Dr. Giesser reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, the earliest detected preclinical phase of multiple sclerosis (MS). Researchers found that dimethyl fumarate reduced the risk of a first acute or progressive event related to CNS demyelination by more than 80%, compared with placebo.
Patients with RIS have incidental MRI abnormalities typical of MS but have no symptoms of the disease. The condition is usually detected when a patient seeks treatment for another issue, such as migraines or head trauma.
The study is the first randomized clinical trial to examine efficacy of a disease-modifying therapy in delaying symptoms in RIS. “It really supports the concept of the benefit of early treatment intervention within this given MS disease spectrum,” lead investigator Darin Okuda, MD, professor of neurology at the University of Texas Southwestern Medical Center in Dallas, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
Topic of debate
RIS was first identified by Dr. Okuda in 2008. Increased use of brain imaging led to the detection of patients with incidental white-matter pathology in the central nervous system on MRI. Some of the findings were nonspecific, but others were highly suggestive of demyelinating pathology based on their location and morphology in the central nervous system.
Although the prevalence of RIS is unknown, incidentally discovered white matter lesions resembling demyelination occur in an estimated 0.1%-0.7% of the general population. Up to half of patients with RIS experience a first clinical MS event within 10 years.
Diagnostic criteria and whether to treat patients with RIS prophylactically has long been a topic of debate among neurologists and radiologists.
Researchers conducted the multicenter, randomized, double-blinded, placebo-controlled ARISE study in 2016, recruiting 87 patients with RIS. The majority of participants were women, and most were diagnosed in their early 40s.
Patients received oral dimethyl fumarate at 240 mg twice daily or placebo and were followed for 96 weeks (1 year, 10 months). Clinical assessments were completed at baseline, at weeks 48 and 96, and at the time of the first clinical event. MRI scans were performed only at the beginning and end of the study.
Those who received dimethyl fumarate had a significantly lower risk of experiencing a first clinical demyelinating event during the study period (adjusted hazard ratio, 0.07; P = .005).
After adjusting for the number of gadolinium-enhancing lesions at baseline, there was a significant reduction in the number of new or newly enlarged T2-weighted hyperintense lesions, a secondary endpoint, in the dimethyl fumarate group, compared with those on placebo (HR, 0.20; P = .042).
“In the future we’d like to see further studies performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time,” Dr. Okuda said.
‘Striking’ findings
Barbara Giesser, MD, a neurologist at Pacific Neuroscience Institute in Santa Monica, Calif., called the results “striking,” but noted that questions remain.
“Up until this study we haven’t had anything like it to guide us in determining whether we should treat RIS or not,” she said. “Obviously, larger studies are needed, but I think this is a very important and well-done study.”
In addition to the small sample size, Dr. Giesser noted that the study lacked data on the presence of risk factors that are known to increase RIS patients’ risk of developing MS, such as evidence of spinal cord lesions. That issue was also raised during discussion of the paper in Amsterdam.
“I don’t think this means you should treat everybody with RIS necessarily,” Dr. Giesser said. “But I think it suggests that in people with RIS, particularly if they do have risk factors, you could consider treatment with dimethyl fumarate.”
The study was funded by Biogen. Dr. Okuda has received support from Biogen and EMD Serono/Merck; and consulting fees from Alexion, Biogen, EMD Serono, Genzyme, Novartis, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, Celgene/Bristol Myers Squibb, Genentech, Janssen Pharmaceuticals, and Osmotica Pharmaceuticals. Dr. Giesser reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2022
‘Reassuring data’ for two MS meds in pregnancy
new research shows. Results of two studies show that preterm birth, spontaneous abortions, and major congenital anomalies were rare with anti-CD20 drugs ocrelizumab or natalizumab, even when continued well into the third trimester. However, hematologic abnormalities were common in newborns who were exposed to MS therapies during pregnancy.
The research comes at a time when the incidence of MS is on the rise worldwide and pregnancy in MS patients is becoming more common (Neurology. 2018 Oct 23;91[17]:e1559-69). “The results of our study should lead to a distinct risk-benefit discussion between neurologists and pregnant natalizumab-treated women to maintain treatment up to the 30th or even the 34th week of gestation, in combination with an early restart during the first 4 weeks after delivery,” Sandra Thiel, PhD, an investigator in one of the studies, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Thiel is in the department of neurology at St. Josef Hospital and Ruhr University Bochum (Germany).
Rising number of pregnancies
In a second study, researchers from Spain presented results from the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS. The trial included 2,020 pregnancies, most of which were followed prospectively. The study included data on pregnancies since 2008. The largest single-year increase among participants was in the past year, in which there was a 65% rise in the number of pregnancies.
“The number of women with MS exposed to ocrelizumab before, during, and after the pregnancy is increasing and increasing,” Celia Oreja-Guevara, MD, PhD, vice-chair of neurology and head of the Multiple Sclerosis Center of the University Hospital San Carlos, Madrid, told conference attendees. “We have more evidence, we have more knowledge, patients and physicians trust ocrelizumab more. They know that it’s a safe treatment, and more patients are becoming pregnant.”
Dr. Oreja-Guevara highlighted a decrease in the number of elective abortions, which dropped from 50% in 2021 to 11% in the past year. The number was higher for patients with known exposure to ocrelizumab (11.5% vs. 3.7%).
Among the prospective cases, ectopic pregnancies occurred in 1.8% of those who were not exposed to ocrelizumab versus 1.4% of those exposed to the medication. The overall rate of spontaneous abortion was 11.8%, which, Dr. Oreja-Guevara said, is lower than the rate among the general population in Spain.
In the total cohort, 79.0% of pregnancies resulted in live births. Rates were similar regardless of ocrelizumab exposure. About 57% of births were full term, and 10.0% were preterm. Gestational age was unknown in 32.9% of the cases.
Overall, 0.9% of infants had a major congenital anomaly, which Dr. Oreja-Guevara said is lower than the rate of 2%-3% in all children born in Europe.
A look at natalizumab
To examine outcomes following use of natalizumab during pregnancy, researchers examined data from the German Multiple Sclerosis and Pregnancy Registry, which was created in 2006 and follows people during pregnancy and up to 6 years post partum. Of the 350 pregnant people included in the study, 171 continued natalizumab therapy beyond the first trimester. Discontinuation occurred at a median of 30.9 gestational weeks.
Most patients did not experience MS relapse during pregnancy, but the number was higher for patients who continued taking natalizumab later into pregnancy compared with those who stopped taking the drug in the first trimester (94.8% vs. 67.6%).
In the group analysis, women who continued treatment after the first trimester had significantly fewer relapses during pregnancy (5.9% vs. 32.4%; P < .001) and in the postpartum period (22.8% vs. 49.7%, P < .001). Resuming treatment with natalizumab within 4 weeks after birth significantly reduced relapse risk post partum (odds ratio, 0.32; P < .001).
The researchers also examined relapse risk with respect to treatment duration after the first trimester. Significantly more women who discontinued natalizumab before the 30th gestational week experienced postpartum relapses, compared with those whose treatment extended beyond that point (38.5% vs. 16.0%; P = .008), especially during the first postpartum trimester (26.9% vs. 8.00%; P = .009).
There were no significant differences in preterm births or major congenital abnormalities between groups. However, about half of the infants exposed to natalizumab beyond the first trimester were born with anemia or other hematologic abnormalities.
Another unexpected finding was the number of infants who were small for their gestational age (SGA). About 19% of infants born to women who continued treatment later in pregnancy were SGA. Among those in the group that discontinued therapy in the first trimester, the figure was just under 17%.
“Pregnancy outcomes were within the expected range, but a potential increased risk for small for gestational age newborns justified further investigation,” Dr. Thiel said.
Reassuring data
Angie Child Jelin, MD, director of the first trimester screening program and associate professor of gynecology and obstetrics at Johns Hopkins University, Baltimore, said that the increase in the number of pregnant patients with MS seen in their clinic could be caused in part by the growing body of work on MS treatment during pregnancy.
“It’s very reassuring that these data have come out and showed how safe they are generally in pregnancy,” Dr. Jalin said.
Although hematologic abnormalities in newborns are thought to be acute, Dr. Jalin said long-term study is needed to better understand any potential lasting effects from those abnormalities, as well as any effects in SGA newborns.
“Long-term outcomes are very hard to acquire, but ideally you’d want long-term outcomes on all of these measures,” Dr. Jalin said.
Funding for the natalizumab study was not disclosed. The ocrelizumab study was funded by F. Hoffmann–La Roche. Dr. Oreja-Guevara received honoraria for consulting and serving on advisory boards from Biogen Idec, F. Hoffmann–La Roche, Genzyme, Merck, Novartis, and Teva. Dr. Thiel has received speaker honoraria from Bayer Healthcare. Dr. Jalin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows. Results of two studies show that preterm birth, spontaneous abortions, and major congenital anomalies were rare with anti-CD20 drugs ocrelizumab or natalizumab, even when continued well into the third trimester. However, hematologic abnormalities were common in newborns who were exposed to MS therapies during pregnancy.
The research comes at a time when the incidence of MS is on the rise worldwide and pregnancy in MS patients is becoming more common (Neurology. 2018 Oct 23;91[17]:e1559-69). “The results of our study should lead to a distinct risk-benefit discussion between neurologists and pregnant natalizumab-treated women to maintain treatment up to the 30th or even the 34th week of gestation, in combination with an early restart during the first 4 weeks after delivery,” Sandra Thiel, PhD, an investigator in one of the studies, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Thiel is in the department of neurology at St. Josef Hospital and Ruhr University Bochum (Germany).
Rising number of pregnancies
In a second study, researchers from Spain presented results from the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS. The trial included 2,020 pregnancies, most of which were followed prospectively. The study included data on pregnancies since 2008. The largest single-year increase among participants was in the past year, in which there was a 65% rise in the number of pregnancies.
“The number of women with MS exposed to ocrelizumab before, during, and after the pregnancy is increasing and increasing,” Celia Oreja-Guevara, MD, PhD, vice-chair of neurology and head of the Multiple Sclerosis Center of the University Hospital San Carlos, Madrid, told conference attendees. “We have more evidence, we have more knowledge, patients and physicians trust ocrelizumab more. They know that it’s a safe treatment, and more patients are becoming pregnant.”
Dr. Oreja-Guevara highlighted a decrease in the number of elective abortions, which dropped from 50% in 2021 to 11% in the past year. The number was higher for patients with known exposure to ocrelizumab (11.5% vs. 3.7%).
Among the prospective cases, ectopic pregnancies occurred in 1.8% of those who were not exposed to ocrelizumab versus 1.4% of those exposed to the medication. The overall rate of spontaneous abortion was 11.8%, which, Dr. Oreja-Guevara said, is lower than the rate among the general population in Spain.
In the total cohort, 79.0% of pregnancies resulted in live births. Rates were similar regardless of ocrelizumab exposure. About 57% of births were full term, and 10.0% were preterm. Gestational age was unknown in 32.9% of the cases.
Overall, 0.9% of infants had a major congenital anomaly, which Dr. Oreja-Guevara said is lower than the rate of 2%-3% in all children born in Europe.
A look at natalizumab
To examine outcomes following use of natalizumab during pregnancy, researchers examined data from the German Multiple Sclerosis and Pregnancy Registry, which was created in 2006 and follows people during pregnancy and up to 6 years post partum. Of the 350 pregnant people included in the study, 171 continued natalizumab therapy beyond the first trimester. Discontinuation occurred at a median of 30.9 gestational weeks.
Most patients did not experience MS relapse during pregnancy, but the number was higher for patients who continued taking natalizumab later into pregnancy compared with those who stopped taking the drug in the first trimester (94.8% vs. 67.6%).
In the group analysis, women who continued treatment after the first trimester had significantly fewer relapses during pregnancy (5.9% vs. 32.4%; P < .001) and in the postpartum period (22.8% vs. 49.7%, P < .001). Resuming treatment with natalizumab within 4 weeks after birth significantly reduced relapse risk post partum (odds ratio, 0.32; P < .001).
The researchers also examined relapse risk with respect to treatment duration after the first trimester. Significantly more women who discontinued natalizumab before the 30th gestational week experienced postpartum relapses, compared with those whose treatment extended beyond that point (38.5% vs. 16.0%; P = .008), especially during the first postpartum trimester (26.9% vs. 8.00%; P = .009).
There were no significant differences in preterm births or major congenital abnormalities between groups. However, about half of the infants exposed to natalizumab beyond the first trimester were born with anemia or other hematologic abnormalities.
Another unexpected finding was the number of infants who were small for their gestational age (SGA). About 19% of infants born to women who continued treatment later in pregnancy were SGA. Among those in the group that discontinued therapy in the first trimester, the figure was just under 17%.
“Pregnancy outcomes were within the expected range, but a potential increased risk for small for gestational age newborns justified further investigation,” Dr. Thiel said.
Reassuring data
Angie Child Jelin, MD, director of the first trimester screening program and associate professor of gynecology and obstetrics at Johns Hopkins University, Baltimore, said that the increase in the number of pregnant patients with MS seen in their clinic could be caused in part by the growing body of work on MS treatment during pregnancy.
“It’s very reassuring that these data have come out and showed how safe they are generally in pregnancy,” Dr. Jalin said.
Although hematologic abnormalities in newborns are thought to be acute, Dr. Jalin said long-term study is needed to better understand any potential lasting effects from those abnormalities, as well as any effects in SGA newborns.
“Long-term outcomes are very hard to acquire, but ideally you’d want long-term outcomes on all of these measures,” Dr. Jalin said.
Funding for the natalizumab study was not disclosed. The ocrelizumab study was funded by F. Hoffmann–La Roche. Dr. Oreja-Guevara received honoraria for consulting and serving on advisory boards from Biogen Idec, F. Hoffmann–La Roche, Genzyme, Merck, Novartis, and Teva. Dr. Thiel has received speaker honoraria from Bayer Healthcare. Dr. Jalin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research shows. Results of two studies show that preterm birth, spontaneous abortions, and major congenital anomalies were rare with anti-CD20 drugs ocrelizumab or natalizumab, even when continued well into the third trimester. However, hematologic abnormalities were common in newborns who were exposed to MS therapies during pregnancy.
The research comes at a time when the incidence of MS is on the rise worldwide and pregnancy in MS patients is becoming more common (Neurology. 2018 Oct 23;91[17]:e1559-69). “The results of our study should lead to a distinct risk-benefit discussion between neurologists and pregnant natalizumab-treated women to maintain treatment up to the 30th or even the 34th week of gestation, in combination with an early restart during the first 4 weeks after delivery,” Sandra Thiel, PhD, an investigator in one of the studies, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Thiel is in the department of neurology at St. Josef Hospital and Ruhr University Bochum (Germany).
Rising number of pregnancies
In a second study, researchers from Spain presented results from the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS. The trial included 2,020 pregnancies, most of which were followed prospectively. The study included data on pregnancies since 2008. The largest single-year increase among participants was in the past year, in which there was a 65% rise in the number of pregnancies.
“The number of women with MS exposed to ocrelizumab before, during, and after the pregnancy is increasing and increasing,” Celia Oreja-Guevara, MD, PhD, vice-chair of neurology and head of the Multiple Sclerosis Center of the University Hospital San Carlos, Madrid, told conference attendees. “We have more evidence, we have more knowledge, patients and physicians trust ocrelizumab more. They know that it’s a safe treatment, and more patients are becoming pregnant.”
Dr. Oreja-Guevara highlighted a decrease in the number of elective abortions, which dropped from 50% in 2021 to 11% in the past year. The number was higher for patients with known exposure to ocrelizumab (11.5% vs. 3.7%).
Among the prospective cases, ectopic pregnancies occurred in 1.8% of those who were not exposed to ocrelizumab versus 1.4% of those exposed to the medication. The overall rate of spontaneous abortion was 11.8%, which, Dr. Oreja-Guevara said, is lower than the rate among the general population in Spain.
In the total cohort, 79.0% of pregnancies resulted in live births. Rates were similar regardless of ocrelizumab exposure. About 57% of births were full term, and 10.0% were preterm. Gestational age was unknown in 32.9% of the cases.
Overall, 0.9% of infants had a major congenital anomaly, which Dr. Oreja-Guevara said is lower than the rate of 2%-3% in all children born in Europe.
A look at natalizumab
To examine outcomes following use of natalizumab during pregnancy, researchers examined data from the German Multiple Sclerosis and Pregnancy Registry, which was created in 2006 and follows people during pregnancy and up to 6 years post partum. Of the 350 pregnant people included in the study, 171 continued natalizumab therapy beyond the first trimester. Discontinuation occurred at a median of 30.9 gestational weeks.
Most patients did not experience MS relapse during pregnancy, but the number was higher for patients who continued taking natalizumab later into pregnancy compared with those who stopped taking the drug in the first trimester (94.8% vs. 67.6%).
In the group analysis, women who continued treatment after the first trimester had significantly fewer relapses during pregnancy (5.9% vs. 32.4%; P < .001) and in the postpartum period (22.8% vs. 49.7%, P < .001). Resuming treatment with natalizumab within 4 weeks after birth significantly reduced relapse risk post partum (odds ratio, 0.32; P < .001).
The researchers also examined relapse risk with respect to treatment duration after the first trimester. Significantly more women who discontinued natalizumab before the 30th gestational week experienced postpartum relapses, compared with those whose treatment extended beyond that point (38.5% vs. 16.0%; P = .008), especially during the first postpartum trimester (26.9% vs. 8.00%; P = .009).
There were no significant differences in preterm births or major congenital abnormalities between groups. However, about half of the infants exposed to natalizumab beyond the first trimester were born with anemia or other hematologic abnormalities.
Another unexpected finding was the number of infants who were small for their gestational age (SGA). About 19% of infants born to women who continued treatment later in pregnancy were SGA. Among those in the group that discontinued therapy in the first trimester, the figure was just under 17%.
“Pregnancy outcomes were within the expected range, but a potential increased risk for small for gestational age newborns justified further investigation,” Dr. Thiel said.
Reassuring data
Angie Child Jelin, MD, director of the first trimester screening program and associate professor of gynecology and obstetrics at Johns Hopkins University, Baltimore, said that the increase in the number of pregnant patients with MS seen in their clinic could be caused in part by the growing body of work on MS treatment during pregnancy.
“It’s very reassuring that these data have come out and showed how safe they are generally in pregnancy,” Dr. Jalin said.
Although hematologic abnormalities in newborns are thought to be acute, Dr. Jalin said long-term study is needed to better understand any potential lasting effects from those abnormalities, as well as any effects in SGA newborns.
“Long-term outcomes are very hard to acquire, but ideally you’d want long-term outcomes on all of these measures,” Dr. Jalin said.
Funding for the natalizumab study was not disclosed. The ocrelizumab study was funded by F. Hoffmann–La Roche. Dr. Oreja-Guevara received honoraria for consulting and serving on advisory boards from Biogen Idec, F. Hoffmann–La Roche, Genzyme, Merck, Novartis, and Teva. Dr. Thiel has received speaker honoraria from Bayer Healthcare. Dr. Jalin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2022
Viagra, Cialis, and Alzheimer’s risk: New data
The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.
The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.
“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.
The new study was published online in Brain Communications.
Not the final word?
Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*
Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.
The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.
In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.
The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.
“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
Impressive study design
Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.
“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”
The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.
The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.
The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.
“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.
The new study was published online in Brain Communications.
Not the final word?
Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*
Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.
The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.
In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.
The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.
“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
Impressive study design
Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.
“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”
The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.
The findings contradict results from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer’s.
The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.
“That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results,” lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women’s Hospital, both in Boston, said in an interview.
The new study was published online in Brain Communications.
Not the final word?
Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.*
Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.
The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED – the most common indication for sildenafil – to generally older individuals with diabetes or hypertension, Dr. Desai said.
In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PDE5 inhibitors. The researchers compared ADRD incidence in those who took PDE5 inhibitors with the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.
The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PDE5 inhibitors.
“No study of this kind should claim the final word,” Dr. Desai said. “It is extremely difficult to nail down causality from these types of data sources.”
Impressive study design
Commenting on the findings, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minn., described the study design as “impressive” for its efforts to minimize bias, a key limitation in the previous study.
“It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials,” Dr. Knopman said. “The evidence for the use of the drug was never sufficient for clinicians to use it in their patients.”
The study was funded by National Institute on Aging. Dr. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women’s Hospital for unrelated projects. Dr. Knopman has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Correction, 11/3/22: An earlier version of this article misstated the abbreviation for phosphodiesterase-5. It is PDE-5.
FROM BRAIN COMMUNICATIONS
Stem cell transplantation ‘substantially’ superior to fingolimod in cutting MS relapse risk
, a new study suggests.
The multicenter observational study showed that AHSCT was associated with a better overall annual relapse rate and significantly greater disability improvement versus fingolimod. Stem cell transplantation also offered a slight advantage compared with natalizumab but showed no benefit over ocrelizumab.
“Based on these results, we can conclude that in this observational study AHSCT is substantially superior to fingolimod and marginally superior to natalizumab in reducing the risk of posttreatment relapses,” study investigator Tomas Kalincik, MD, PhD, said at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Research gap
Prior studies have suggested that AHSCT is associated with better disability outcomes than other immunotherapies in patients with active secondary progressive MS. Findings from another study on long-term efficacy in relapse prevention are also promising.
“The information that we are still lacking is the head-to-head comparison of the effectiveness of AHSCT in relapsing-remitting disease to concrete, highly effective therapies, which is the aim of this current study,” said Dr. Kalincik, professor of neurology at the University of Melbourne and head of the Multiple Sclerosis and Neuroimmunology Service at the Royal Melbourne Hospital, Australia.
The study included 167 patients with relapsing-remitting MS from six centers in Ottawa, Uppsala, Sheffield, Bergen, Sydney, and Melbourne, combined with 1,675 patients from MSBase. Patients were included if they were treated with AHSCT or fingolimod (n = 769), natalizumab (n = 730) or ocrelizumab (n = 343).
Researchers used propensity matching to ensure the AHSCT and disease-modifying therapy (DMT) groups had similar relapse rates and disability scores at baseline. At 1 year, patients who underwent AHSCT were 74% more likely than were those on fingolimod to be relapse free (hazard ratio [HR], 0.26; P < .0001).
The AHSCT group had a lower overall annualized relapse rate (0.09 vs. 0.19, respectively; P < .0001) and a higher cumulative probability of remaining relapse free at 2 years (90% vs. 68%, respectively) and 5 years (85% vs. 54%, respectively). AHSCT was associated with significantly better confirmed disability improvement at 6 months compared with fingolimod (HR, 2.70; P < .0001).
The researchers found better outcomes with AHSCT compared with natalizumab, but the results weren’t as promising. The annual relapse rate with AHSCT was statistically significant (P = .03) but the clinical benefit was marginal, Dr. Kalincik said. However, the confirmed disability improvement was significantly better with AHSCT (HR, 2.68; P < .0001).
There was no significant difference in outcomes with AHSCT compared to ocrelizumab.
Adverse events were common with stem cell transplantation, a sticking point for at least one conference attendee who raised safety concerns. Among those treated with AHSCT, 23% had febrile neutropenia, 11% had serum sickness, and 36% experienced complications after discharge, mostly infection. There was one AHSCT treatment-related death.
“We’re showing that AHSCT is a highly potent therapy that definitely is competitive vis a vis the most potent standard conventional disease modifying therapies,” said Dr. Kalincik, who noted the high rate of adverse events. Still, treatment-related mortality from AHSCT has improved since the therapy was first used in MS patients, he added.
“I’m hoping the data provides some evidence to convince you that this treatment still has a place in our armamentarium,” Dr. Kalincik said.
Questions remain
Eva Kubala Havrdová, MD, PhD, professor of neurology in the Multiple Sclerosis Center at Charles University in Prague, Czech Republic, said the results add to a growing body of data on the efficacy of AHSCT in patients with highly active relapsing-remitting MS, but questions remain.
“It is important to understand that AHSCT provides advantage in terms of effectiveness compared with most of the DMTs,” Dr. Kubala Havrdová said. “However, it is a therapy associated with high risk of adverse events and this needs to be considered when one decides whether other, less invasive options have been exploited.”
Study funding was not reported. Dr. Kalincik disclosed ties with BioCSL, Biogen, BMS, Celgene, Eisai, Janssen, Merck, Novartis, Roche, Sanofi Genzyme, Teva, and WebMD Global. Dr. Kubala Havrdová reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The multicenter observational study showed that AHSCT was associated with a better overall annual relapse rate and significantly greater disability improvement versus fingolimod. Stem cell transplantation also offered a slight advantage compared with natalizumab but showed no benefit over ocrelizumab.
“Based on these results, we can conclude that in this observational study AHSCT is substantially superior to fingolimod and marginally superior to natalizumab in reducing the risk of posttreatment relapses,” study investigator Tomas Kalincik, MD, PhD, said at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Research gap
Prior studies have suggested that AHSCT is associated with better disability outcomes than other immunotherapies in patients with active secondary progressive MS. Findings from another study on long-term efficacy in relapse prevention are also promising.
“The information that we are still lacking is the head-to-head comparison of the effectiveness of AHSCT in relapsing-remitting disease to concrete, highly effective therapies, which is the aim of this current study,” said Dr. Kalincik, professor of neurology at the University of Melbourne and head of the Multiple Sclerosis and Neuroimmunology Service at the Royal Melbourne Hospital, Australia.
The study included 167 patients with relapsing-remitting MS from six centers in Ottawa, Uppsala, Sheffield, Bergen, Sydney, and Melbourne, combined with 1,675 patients from MSBase. Patients were included if they were treated with AHSCT or fingolimod (n = 769), natalizumab (n = 730) or ocrelizumab (n = 343).
Researchers used propensity matching to ensure the AHSCT and disease-modifying therapy (DMT) groups had similar relapse rates and disability scores at baseline. At 1 year, patients who underwent AHSCT were 74% more likely than were those on fingolimod to be relapse free (hazard ratio [HR], 0.26; P < .0001).
The AHSCT group had a lower overall annualized relapse rate (0.09 vs. 0.19, respectively; P < .0001) and a higher cumulative probability of remaining relapse free at 2 years (90% vs. 68%, respectively) and 5 years (85% vs. 54%, respectively). AHSCT was associated with significantly better confirmed disability improvement at 6 months compared with fingolimod (HR, 2.70; P < .0001).
The researchers found better outcomes with AHSCT compared with natalizumab, but the results weren’t as promising. The annual relapse rate with AHSCT was statistically significant (P = .03) but the clinical benefit was marginal, Dr. Kalincik said. However, the confirmed disability improvement was significantly better with AHSCT (HR, 2.68; P < .0001).
There was no significant difference in outcomes with AHSCT compared to ocrelizumab.
Adverse events were common with stem cell transplantation, a sticking point for at least one conference attendee who raised safety concerns. Among those treated with AHSCT, 23% had febrile neutropenia, 11% had serum sickness, and 36% experienced complications after discharge, mostly infection. There was one AHSCT treatment-related death.
“We’re showing that AHSCT is a highly potent therapy that definitely is competitive vis a vis the most potent standard conventional disease modifying therapies,” said Dr. Kalincik, who noted the high rate of adverse events. Still, treatment-related mortality from AHSCT has improved since the therapy was first used in MS patients, he added.
“I’m hoping the data provides some evidence to convince you that this treatment still has a place in our armamentarium,” Dr. Kalincik said.
Questions remain
Eva Kubala Havrdová, MD, PhD, professor of neurology in the Multiple Sclerosis Center at Charles University in Prague, Czech Republic, said the results add to a growing body of data on the efficacy of AHSCT in patients with highly active relapsing-remitting MS, but questions remain.
“It is important to understand that AHSCT provides advantage in terms of effectiveness compared with most of the DMTs,” Dr. Kubala Havrdová said. “However, it is a therapy associated with high risk of adverse events and this needs to be considered when one decides whether other, less invasive options have been exploited.”
Study funding was not reported. Dr. Kalincik disclosed ties with BioCSL, Biogen, BMS, Celgene, Eisai, Janssen, Merck, Novartis, Roche, Sanofi Genzyme, Teva, and WebMD Global. Dr. Kubala Havrdová reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The multicenter observational study showed that AHSCT was associated with a better overall annual relapse rate and significantly greater disability improvement versus fingolimod. Stem cell transplantation also offered a slight advantage compared with natalizumab but showed no benefit over ocrelizumab.
“Based on these results, we can conclude that in this observational study AHSCT is substantially superior to fingolimod and marginally superior to natalizumab in reducing the risk of posttreatment relapses,” study investigator Tomas Kalincik, MD, PhD, said at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Research gap
Prior studies have suggested that AHSCT is associated with better disability outcomes than other immunotherapies in patients with active secondary progressive MS. Findings from another study on long-term efficacy in relapse prevention are also promising.
“The information that we are still lacking is the head-to-head comparison of the effectiveness of AHSCT in relapsing-remitting disease to concrete, highly effective therapies, which is the aim of this current study,” said Dr. Kalincik, professor of neurology at the University of Melbourne and head of the Multiple Sclerosis and Neuroimmunology Service at the Royal Melbourne Hospital, Australia.
The study included 167 patients with relapsing-remitting MS from six centers in Ottawa, Uppsala, Sheffield, Bergen, Sydney, and Melbourne, combined with 1,675 patients from MSBase. Patients were included if they were treated with AHSCT or fingolimod (n = 769), natalizumab (n = 730) or ocrelizumab (n = 343).
Researchers used propensity matching to ensure the AHSCT and disease-modifying therapy (DMT) groups had similar relapse rates and disability scores at baseline. At 1 year, patients who underwent AHSCT were 74% more likely than were those on fingolimod to be relapse free (hazard ratio [HR], 0.26; P < .0001).
The AHSCT group had a lower overall annualized relapse rate (0.09 vs. 0.19, respectively; P < .0001) and a higher cumulative probability of remaining relapse free at 2 years (90% vs. 68%, respectively) and 5 years (85% vs. 54%, respectively). AHSCT was associated with significantly better confirmed disability improvement at 6 months compared with fingolimod (HR, 2.70; P < .0001).
The researchers found better outcomes with AHSCT compared with natalizumab, but the results weren’t as promising. The annual relapse rate with AHSCT was statistically significant (P = .03) but the clinical benefit was marginal, Dr. Kalincik said. However, the confirmed disability improvement was significantly better with AHSCT (HR, 2.68; P < .0001).
There was no significant difference in outcomes with AHSCT compared to ocrelizumab.
Adverse events were common with stem cell transplantation, a sticking point for at least one conference attendee who raised safety concerns. Among those treated with AHSCT, 23% had febrile neutropenia, 11% had serum sickness, and 36% experienced complications after discharge, mostly infection. There was one AHSCT treatment-related death.
“We’re showing that AHSCT is a highly potent therapy that definitely is competitive vis a vis the most potent standard conventional disease modifying therapies,” said Dr. Kalincik, who noted the high rate of adverse events. Still, treatment-related mortality from AHSCT has improved since the therapy was first used in MS patients, he added.
“I’m hoping the data provides some evidence to convince you that this treatment still has a place in our armamentarium,” Dr. Kalincik said.
Questions remain
Eva Kubala Havrdová, MD, PhD, professor of neurology in the Multiple Sclerosis Center at Charles University in Prague, Czech Republic, said the results add to a growing body of data on the efficacy of AHSCT in patients with highly active relapsing-remitting MS, but questions remain.
“It is important to understand that AHSCT provides advantage in terms of effectiveness compared with most of the DMTs,” Dr. Kubala Havrdová said. “However, it is a therapy associated with high risk of adverse events and this needs to be considered when one decides whether other, less invasive options have been exploited.”
Study funding was not reported. Dr. Kalincik disclosed ties with BioCSL, Biogen, BMS, Celgene, Eisai, Janssen, Merck, Novartis, Roche, Sanofi Genzyme, Teva, and WebMD Global. Dr. Kubala Havrdová reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2022
Self-worth training boosts ketamine’s effects in severe depression
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The double-blind, randomized clinical trial is the first to assess combining ketamine with a low-cost protective learning program, researchers note.
They add that the findings are an important step toward long-lasting depression treatment for millions of patients whose depression does not improve following first-line therapies.
“One of the biggest challenges in psychiatry and psychology is seeing evidence of longer-term benefits and longer-term compliance,” lead investigator Rebecca B. Price, PhD, associate professor of psychiatry and psychology, University of Pittsburgh, told this news organization.
“Anything that can get somebody well quickly and keep them well for some length of time is really exciting – and a whole paradigm shift for how things have been done up to now,” Dr. Price said.
The findings were published online in the American Journal of Psychiatry.
Promoting self-worth
About one-third of patients with depression remain treatment-resistant even after trying different medications at different doses and at different combinations, the investigators note.
Ketamine and esketamine, a nasal spray formulation of the drug, have been shown previously to improve symptoms in patients with TRD. While the benefits are evident within a few hours of treatment, the effects often wane after just a few weeks.
Ketamine and esketamine must be administered in a clinical setting and patients must be monitored for at least 2 hours after treatment. Repeat dosing is costly, both in time and expense, so clinical researchers have been studying ways to extend the drug’s effects without additional treatments.
The new study combined ketamine treatment with a computer-based active automated self-association training (ASAT) program that the researchers developed. It uses positive words and imagery to promote positive self-image and self-worth.
The trial included 154 adults with treatment-resistant unipolar depression whose symptoms persisted after therapy with at least two medications. Participants received an IV infusion of ketamine 0.5 mg/kg plus active ASAT (n = 53), saline plus active ASAT (n = 51), or ketamine plus sham ASAT (n = 50).
The active program used words like “sweet,” “lovable,” and “worthy” that appeared on the screen interspersed with images of people smiling and the patient’s own photo. Participants were also asked to complete certain mouse-tracking tasks during the session.
The sham ASAT was similar but included neutral words and images. ASAT and sham ASAT were delivered twice daily over 4 consecutive days for 20 minutes.
Clear benefit
Results showed that ketamine rapidly and significantly reduced depression scores within 24 hours of treatment (group-by-time interaction: standardized beta, –1.30; 95% confidence interval, –1.89 to –0.70).
Depression scores in the ketamine-plus-ASAT group remained low and stable over a 30-day period, compared with the saline-plus-ASAT group (standardized beta, –0.61; 95% CI, –0.95 to –0.28).
Participants who received ketamine plus sham ASAT saw initial improvement in symptoms immediately following infusion, but depression symptoms returned after a few weeks.
While researchers hoped to see positive effects from ASAT, “I certainly did not expect to see something so clear to jump right out,” Dr. Price said.
The investigators are now examining whether the computer program can be administered effectively remotely and whether its effects are equally beneficial following treatment with esketamine.
Greatest unmet need
Gerard Sanacora, MD, PhD, professor of psychiatry, and director, Yale Depression Research Program, Yale University, New Haven, Conn., said that extending the effects of ketamine or esketamine without additional dosing is “probably the greatest unmet need in relation to treatments with ketamine and esketamine.”
He added that there are large economic, time, and access burdens associated with the treatment of ketamine.
“Anything we can do to reduce the number of treatments needed or increase the sustainability or the duration of effect would be a tremendous benefit,” said Dr. Sanacora, who was not involved with the research.
Adding an easily accessible, nonpharmacological therapeutic approach to ketamine treatment could be valuable, he said – but more research is needed.
“I’m not sure that this specific associated positive thinking is really the critical component. I think we still have some work to do there. But it does demonstrate that we can use ancillary or augmenting nonpharmacological treatments to extend the effect,” Dr. Sanacora said.
The study was funded by the National Institute of Mental Health and Clinical and Translational Science Institute at the University of Pittsburgh. Dr. Price is the named inventor on a University of Pittsburgh–owned provisional patent filing related to the combination intervention described in this report. Dr. Sanacora reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PSYCHIATRY