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AHA: Quality of STEMI care has stalled, needs improvement
Following up on its 2007 initiative to improve care for people who have ST-segment elevation myocardial infarction (STEMI), the American Heart Association has issued a policy statement that includes a host of recommendations to further overcome barriers to optimal care for this most severe type of heart attack.
The statement recommends steps for designing what the writing committee calls “the ideal STEMI system of care” for patients who have these severe heart attacks.
The focus of the policy statement is the AHA’s Mission: Lifeline national initiative to coordinate and improve the quality of care to patients with STEMI, which was introduced in 2007. Since then, the number or participating hospitals has increased from 485 to 857, now covering more than 85% of the U.S. population, noted the new statement, published online in Circulation.
“Bringing STEMI referring hospitals, STEMI receiving centers and emergency medical services [EMS] together in the development of local and regional systems of care within the AHA’s Mission: Lifeline program has led to significant improvement in time to treatment and outcomes for patients with STEMI,” Alice K. Jacobs, MD, lead statement author and vice chair for clinical affairs in the department of medicine at Boston Medical Center and a professor at Boston University, said in an interview.
“Yet,” Dr. Jacobs added, “opportunities exist to further improve the coordination of care and address remaining barriers to providing ideal care. Moreover, Mission: Lifeline systems of care have been extended to other time-sensitive cardiovascular disorders including stroke and out-of-hospital cardiac arrest.”
The statement itself noted, “Although there have been significant improvements in patients with STEMI receiving guideline-recommended care, progress has slowed during the past few years.” From 2008 to 2012, a number of key quality care measures at participating hospitals had improved markedly. For example, door-in-door-out (DIDO) transfers improved from a median of 76 to 62 minutes (P < .001).
However, from 2012 to 2019, with more hospitals participating, while many key measures improved, a few either plateaued or worsened slightly. Median DIDO time, for example – again, with more hospitals participating, compared with the earlier dataset – went from 45 in 2012 to 48 in 2019, according to AHA data.
Key recommendations aim to impact and improve hospital care for patients with STEMI, Dr. Jacobs said. “In addition to avoiding patient delay at the onset of recognized symptoms of a heart attack, accessing 911 and following EMS destination protocols, the prehospital activation of the cardiac catheterization lab and providing a 911 response for interhospital transport as well as direct-to-cardiac-catheterization-lab transport bypassing the emergency department when appropriate would all impact and improve hospital care.”
Other key recommendations of the statement include:
- Increasing public awareness of heart attack signs and symptoms and the importance for calling 911.
- Addressing post-MI care, including use of evidence-based practices for cardiac rehabilitation and even getting insurance companies to encourage cardiac rehab through incentives.
- Engaging rural hospitals by leveraging telemedicine to expedite percutaneous coronary intervention (PCI) and by developing systems for treatment protocols and rapid transport among facilities.
- Tearing down financial barriers with a global reimbursement model that encompasses each stop in a patient’s journey through the care system: the referring hospital, receiving center, EMS transport and transfer, and ancillary services.
The statement also took into account improving disparities in the quality of care women with STEMI receive. “It has been reported that women with STEMI may have less typical symptoms than men and arrive later [delay longer] than men after symptom onset,” Dr. Jacobs said. “Educating the public and all members of the health-care team about issues specific to women will be helpful in improving care in women. Of note, STEMI systems of care have been shown to reduce sex and age disparities in care.”
The statement also addressed implications of the COVID-19 pandemic, stating that PCI should remain the dominant treatment for patients with classic STEMI. “Patients must be reassured that appropriate precautions have been implemented by EMS and hospital to protect them and health care workers from COVID-19 infection,” the statement noted.
Dr. Jacobs has no relevant relationships to disclose.
Following up on its 2007 initiative to improve care for people who have ST-segment elevation myocardial infarction (STEMI), the American Heart Association has issued a policy statement that includes a host of recommendations to further overcome barriers to optimal care for this most severe type of heart attack.
The statement recommends steps for designing what the writing committee calls “the ideal STEMI system of care” for patients who have these severe heart attacks.
The focus of the policy statement is the AHA’s Mission: Lifeline national initiative to coordinate and improve the quality of care to patients with STEMI, which was introduced in 2007. Since then, the number or participating hospitals has increased from 485 to 857, now covering more than 85% of the U.S. population, noted the new statement, published online in Circulation.
“Bringing STEMI referring hospitals, STEMI receiving centers and emergency medical services [EMS] together in the development of local and regional systems of care within the AHA’s Mission: Lifeline program has led to significant improvement in time to treatment and outcomes for patients with STEMI,” Alice K. Jacobs, MD, lead statement author and vice chair for clinical affairs in the department of medicine at Boston Medical Center and a professor at Boston University, said in an interview.
“Yet,” Dr. Jacobs added, “opportunities exist to further improve the coordination of care and address remaining barriers to providing ideal care. Moreover, Mission: Lifeline systems of care have been extended to other time-sensitive cardiovascular disorders including stroke and out-of-hospital cardiac arrest.”
The statement itself noted, “Although there have been significant improvements in patients with STEMI receiving guideline-recommended care, progress has slowed during the past few years.” From 2008 to 2012, a number of key quality care measures at participating hospitals had improved markedly. For example, door-in-door-out (DIDO) transfers improved from a median of 76 to 62 minutes (P < .001).
However, from 2012 to 2019, with more hospitals participating, while many key measures improved, a few either plateaued or worsened slightly. Median DIDO time, for example – again, with more hospitals participating, compared with the earlier dataset – went from 45 in 2012 to 48 in 2019, according to AHA data.
Key recommendations aim to impact and improve hospital care for patients with STEMI, Dr. Jacobs said. “In addition to avoiding patient delay at the onset of recognized symptoms of a heart attack, accessing 911 and following EMS destination protocols, the prehospital activation of the cardiac catheterization lab and providing a 911 response for interhospital transport as well as direct-to-cardiac-catheterization-lab transport bypassing the emergency department when appropriate would all impact and improve hospital care.”
Other key recommendations of the statement include:
- Increasing public awareness of heart attack signs and symptoms and the importance for calling 911.
- Addressing post-MI care, including use of evidence-based practices for cardiac rehabilitation and even getting insurance companies to encourage cardiac rehab through incentives.
- Engaging rural hospitals by leveraging telemedicine to expedite percutaneous coronary intervention (PCI) and by developing systems for treatment protocols and rapid transport among facilities.
- Tearing down financial barriers with a global reimbursement model that encompasses each stop in a patient’s journey through the care system: the referring hospital, receiving center, EMS transport and transfer, and ancillary services.
The statement also took into account improving disparities in the quality of care women with STEMI receive. “It has been reported that women with STEMI may have less typical symptoms than men and arrive later [delay longer] than men after symptom onset,” Dr. Jacobs said. “Educating the public and all members of the health-care team about issues specific to women will be helpful in improving care in women. Of note, STEMI systems of care have been shown to reduce sex and age disparities in care.”
The statement also addressed implications of the COVID-19 pandemic, stating that PCI should remain the dominant treatment for patients with classic STEMI. “Patients must be reassured that appropriate precautions have been implemented by EMS and hospital to protect them and health care workers from COVID-19 infection,” the statement noted.
Dr. Jacobs has no relevant relationships to disclose.
Following up on its 2007 initiative to improve care for people who have ST-segment elevation myocardial infarction (STEMI), the American Heart Association has issued a policy statement that includes a host of recommendations to further overcome barriers to optimal care for this most severe type of heart attack.
The statement recommends steps for designing what the writing committee calls “the ideal STEMI system of care” for patients who have these severe heart attacks.
The focus of the policy statement is the AHA’s Mission: Lifeline national initiative to coordinate and improve the quality of care to patients with STEMI, which was introduced in 2007. Since then, the number or participating hospitals has increased from 485 to 857, now covering more than 85% of the U.S. population, noted the new statement, published online in Circulation.
“Bringing STEMI referring hospitals, STEMI receiving centers and emergency medical services [EMS] together in the development of local and regional systems of care within the AHA’s Mission: Lifeline program has led to significant improvement in time to treatment and outcomes for patients with STEMI,” Alice K. Jacobs, MD, lead statement author and vice chair for clinical affairs in the department of medicine at Boston Medical Center and a professor at Boston University, said in an interview.
“Yet,” Dr. Jacobs added, “opportunities exist to further improve the coordination of care and address remaining barriers to providing ideal care. Moreover, Mission: Lifeline systems of care have been extended to other time-sensitive cardiovascular disorders including stroke and out-of-hospital cardiac arrest.”
The statement itself noted, “Although there have been significant improvements in patients with STEMI receiving guideline-recommended care, progress has slowed during the past few years.” From 2008 to 2012, a number of key quality care measures at participating hospitals had improved markedly. For example, door-in-door-out (DIDO) transfers improved from a median of 76 to 62 minutes (P < .001).
However, from 2012 to 2019, with more hospitals participating, while many key measures improved, a few either plateaued or worsened slightly. Median DIDO time, for example – again, with more hospitals participating, compared with the earlier dataset – went from 45 in 2012 to 48 in 2019, according to AHA data.
Key recommendations aim to impact and improve hospital care for patients with STEMI, Dr. Jacobs said. “In addition to avoiding patient delay at the onset of recognized symptoms of a heart attack, accessing 911 and following EMS destination protocols, the prehospital activation of the cardiac catheterization lab and providing a 911 response for interhospital transport as well as direct-to-cardiac-catheterization-lab transport bypassing the emergency department when appropriate would all impact and improve hospital care.”
Other key recommendations of the statement include:
- Increasing public awareness of heart attack signs and symptoms and the importance for calling 911.
- Addressing post-MI care, including use of evidence-based practices for cardiac rehabilitation and even getting insurance companies to encourage cardiac rehab through incentives.
- Engaging rural hospitals by leveraging telemedicine to expedite percutaneous coronary intervention (PCI) and by developing systems for treatment protocols and rapid transport among facilities.
- Tearing down financial barriers with a global reimbursement model that encompasses each stop in a patient’s journey through the care system: the referring hospital, receiving center, EMS transport and transfer, and ancillary services.
The statement also took into account improving disparities in the quality of care women with STEMI receive. “It has been reported that women with STEMI may have less typical symptoms than men and arrive later [delay longer] than men after symptom onset,” Dr. Jacobs said. “Educating the public and all members of the health-care team about issues specific to women will be helpful in improving care in women. Of note, STEMI systems of care have been shown to reduce sex and age disparities in care.”
The statement also addressed implications of the COVID-19 pandemic, stating that PCI should remain the dominant treatment for patients with classic STEMI. “Patients must be reassured that appropriate precautions have been implemented by EMS and hospital to protect them and health care workers from COVID-19 infection,” the statement noted.
Dr. Jacobs has no relevant relationships to disclose.
FROM CIRCULATION
Study identifies pandemic-related stressor in Parkinson’s disease
a team of researchers in the Netherlands reported, but they also identified meaningful targets for intervention.
Lisanne Dommershuijsen, MSc, a PhD candidate and researcher in epidemiology at the Erasmus University Medical Center in Rotterdam, the Netherlands, reported on a cross-sectional study of 833 participants with Parkinson’s disease in the PRIME-NL study at the International Congress of Parkinson’s Disease and Movement Disorders. The average age of participants was 70.2 and 38% were women.
“We studied targeted hypothetical interventions on COVID-19 stressors in people with Parkinson’s disease,” Ms. Dommershuijsen said. “This disruption in normal life caused considerable psychological stress in community-dwelling individuals. People with Parkinson’s disease might be especially vulnerable to this stress.
“For instance, because reduced levels of physical activity have worsened symptoms or because people with Parkinson’s often have difficulty with flexible [adaptations] to drastic and rapid changes in daily routines, such as those introduced by the COVID-19 pandemic, previous studies found that COVID-19 worsened depression and anxiety symptoms and reduced quality of life (QOL) in people with Parkinson’s disease,” Ms. Dommershuijsen said.
Hence, the goal of the study was to identify the most vulnerable subgroups in the Parkinson’s population and to suggest potential interventions to ameliorate these impacts, she said.
The study focused on eight different stressors that emerged in the pandemic: access to care, medicine and nursing services; loss of social contact; canceled social events; tension or conflict in the home; inability to perform physical activity or relax; and COVID-19 symptoms. The outcomes of interest were depression, as measured with the Beck Depression Inventory (BDI); anxiety, as measured with the Spielberger State-Trait Anxiety Inventory (STAI); and QOL, with the Parkinson’s Disease Quality of Life Questionnaire. The aggregate resulted in a scale of 0-40, with the mean stressor score in the study being 9.6, Ms. Dommershuijsen said.
The BDI and STAI scores for social stressors – loss of social contacts, social events canceled and tension or conflict at home – exceeded those for the so-called care stressors – problems accessing care, medication or nursing – she said, although all eight stressors yielded higher BDI and STAI scores across the board.
Vulnerable subgroups
“When we looked at vulnerable subgroups of people with Parkinson’s disease, we found more pronounced associations between the COVID-19 stress and mental health in women, in highly educated participants, and in participants with advanced Parkinson’s disease,” Ms. Dommershuijsen said. The impact on women and people with advanced disease is explainable, Ms. Dommershuijsen added in an interview; the former because depressive symptoms are more common in women, and the latter because loss of access to care impacts mental wellness.
“The finding that social stressors were more related to anxiety in highly educated people was surprising to us, given that depression in general is more common in people with a lower education,” she said in an interview. “One previous study of the general population suggested this might be related to expectations about available resources, but this findings and the possible explanation warrants further investigation.”
When the study stratified for coping strategies, the COVID-19 stressors had a smaller effect on depressive and anxiety symptoms in Parkinson’s disease patients prone to confrontive coping and planful problem solving, she said. “Whereas, we observed a larger effect of these stressors in people who are prone to using distancing or seeking social support as coping mechanisms,” Ms. Dommershuijsen said.
The researchers also created a model of a hypothetical 50% reduction in COVID-19 stressors among all study participants, but the effect wasn’t clinically relevant, Ms. Dommershuijsen said. However, in people with advanced Parkinson’s disease – that is, with an Movement Disorder Society–Unified Parkinson Disease Rating Scale score above median – the effect was clinically relevant in all outcomes.
The potential interventions the study identified were telemedicine via virtual consultations to alleviate care stressors, and virtual support groups and online classes to address social stressors. “However, a more personalized approach is needed to target tension or conflict at home, which was the most important social stressor influencing depression and anxiety symptoms in our study,” she said. “Social work can play an important role here.”
Asked to comment on the study, Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, said in an interview that the findings align with his research on the impact of COVID-19 and related restrictions on people with Parkinson’s disease.
“The pandemic has affected people in different ways,” he said. “Initially very acutely, people just didn’t have access to doctors. There was also the acute question in movement disorders, but also in other diseases where the people with Parkinson’s disease are going to have the worse outcome when they have COVID-19.” Dr. Alcalay authored two recent papers on the impact of COVID-19 in people with Parkinson’s disease.
“Then we see that, in addition to that question, there’s the question of even if they don’t have COVID-19, just the social distancing and the lack of access to health care, and specifically to physical and occupational therapy and other services, can be quite damaging,” he said.
What’s commendable about the study, he said, was that it just doesn’t highlight the problem. “They’re also highlighting potential solutions, that planful problem solving and coping strategies can be helpful to people.”
Neither Ms. Dommershuijsen nor Dr. Alcalay have any relevant relationships to disclose.
a team of researchers in the Netherlands reported, but they also identified meaningful targets for intervention.
Lisanne Dommershuijsen, MSc, a PhD candidate and researcher in epidemiology at the Erasmus University Medical Center in Rotterdam, the Netherlands, reported on a cross-sectional study of 833 participants with Parkinson’s disease in the PRIME-NL study at the International Congress of Parkinson’s Disease and Movement Disorders. The average age of participants was 70.2 and 38% were women.
“We studied targeted hypothetical interventions on COVID-19 stressors in people with Parkinson’s disease,” Ms. Dommershuijsen said. “This disruption in normal life caused considerable psychological stress in community-dwelling individuals. People with Parkinson’s disease might be especially vulnerable to this stress.
“For instance, because reduced levels of physical activity have worsened symptoms or because people with Parkinson’s often have difficulty with flexible [adaptations] to drastic and rapid changes in daily routines, such as those introduced by the COVID-19 pandemic, previous studies found that COVID-19 worsened depression and anxiety symptoms and reduced quality of life (QOL) in people with Parkinson’s disease,” Ms. Dommershuijsen said.
Hence, the goal of the study was to identify the most vulnerable subgroups in the Parkinson’s population and to suggest potential interventions to ameliorate these impacts, she said.
The study focused on eight different stressors that emerged in the pandemic: access to care, medicine and nursing services; loss of social contact; canceled social events; tension or conflict in the home; inability to perform physical activity or relax; and COVID-19 symptoms. The outcomes of interest were depression, as measured with the Beck Depression Inventory (BDI); anxiety, as measured with the Spielberger State-Trait Anxiety Inventory (STAI); and QOL, with the Parkinson’s Disease Quality of Life Questionnaire. The aggregate resulted in a scale of 0-40, with the mean stressor score in the study being 9.6, Ms. Dommershuijsen said.
The BDI and STAI scores for social stressors – loss of social contacts, social events canceled and tension or conflict at home – exceeded those for the so-called care stressors – problems accessing care, medication or nursing – she said, although all eight stressors yielded higher BDI and STAI scores across the board.
Vulnerable subgroups
“When we looked at vulnerable subgroups of people with Parkinson’s disease, we found more pronounced associations between the COVID-19 stress and mental health in women, in highly educated participants, and in participants with advanced Parkinson’s disease,” Ms. Dommershuijsen said. The impact on women and people with advanced disease is explainable, Ms. Dommershuijsen added in an interview; the former because depressive symptoms are more common in women, and the latter because loss of access to care impacts mental wellness.
“The finding that social stressors were more related to anxiety in highly educated people was surprising to us, given that depression in general is more common in people with a lower education,” she said in an interview. “One previous study of the general population suggested this might be related to expectations about available resources, but this findings and the possible explanation warrants further investigation.”
When the study stratified for coping strategies, the COVID-19 stressors had a smaller effect on depressive and anxiety symptoms in Parkinson’s disease patients prone to confrontive coping and planful problem solving, she said. “Whereas, we observed a larger effect of these stressors in people who are prone to using distancing or seeking social support as coping mechanisms,” Ms. Dommershuijsen said.
The researchers also created a model of a hypothetical 50% reduction in COVID-19 stressors among all study participants, but the effect wasn’t clinically relevant, Ms. Dommershuijsen said. However, in people with advanced Parkinson’s disease – that is, with an Movement Disorder Society–Unified Parkinson Disease Rating Scale score above median – the effect was clinically relevant in all outcomes.
The potential interventions the study identified were telemedicine via virtual consultations to alleviate care stressors, and virtual support groups and online classes to address social stressors. “However, a more personalized approach is needed to target tension or conflict at home, which was the most important social stressor influencing depression and anxiety symptoms in our study,” she said. “Social work can play an important role here.”
Asked to comment on the study, Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, said in an interview that the findings align with his research on the impact of COVID-19 and related restrictions on people with Parkinson’s disease.
“The pandemic has affected people in different ways,” he said. “Initially very acutely, people just didn’t have access to doctors. There was also the acute question in movement disorders, but also in other diseases where the people with Parkinson’s disease are going to have the worse outcome when they have COVID-19.” Dr. Alcalay authored two recent papers on the impact of COVID-19 in people with Parkinson’s disease.
“Then we see that, in addition to that question, there’s the question of even if they don’t have COVID-19, just the social distancing and the lack of access to health care, and specifically to physical and occupational therapy and other services, can be quite damaging,” he said.
What’s commendable about the study, he said, was that it just doesn’t highlight the problem. “They’re also highlighting potential solutions, that planful problem solving and coping strategies can be helpful to people.”
Neither Ms. Dommershuijsen nor Dr. Alcalay have any relevant relationships to disclose.
a team of researchers in the Netherlands reported, but they also identified meaningful targets for intervention.
Lisanne Dommershuijsen, MSc, a PhD candidate and researcher in epidemiology at the Erasmus University Medical Center in Rotterdam, the Netherlands, reported on a cross-sectional study of 833 participants with Parkinson’s disease in the PRIME-NL study at the International Congress of Parkinson’s Disease and Movement Disorders. The average age of participants was 70.2 and 38% were women.
“We studied targeted hypothetical interventions on COVID-19 stressors in people with Parkinson’s disease,” Ms. Dommershuijsen said. “This disruption in normal life caused considerable psychological stress in community-dwelling individuals. People with Parkinson’s disease might be especially vulnerable to this stress.
“For instance, because reduced levels of physical activity have worsened symptoms or because people with Parkinson’s often have difficulty with flexible [adaptations] to drastic and rapid changes in daily routines, such as those introduced by the COVID-19 pandemic, previous studies found that COVID-19 worsened depression and anxiety symptoms and reduced quality of life (QOL) in people with Parkinson’s disease,” Ms. Dommershuijsen said.
Hence, the goal of the study was to identify the most vulnerable subgroups in the Parkinson’s population and to suggest potential interventions to ameliorate these impacts, she said.
The study focused on eight different stressors that emerged in the pandemic: access to care, medicine and nursing services; loss of social contact; canceled social events; tension or conflict in the home; inability to perform physical activity or relax; and COVID-19 symptoms. The outcomes of interest were depression, as measured with the Beck Depression Inventory (BDI); anxiety, as measured with the Spielberger State-Trait Anxiety Inventory (STAI); and QOL, with the Parkinson’s Disease Quality of Life Questionnaire. The aggregate resulted in a scale of 0-40, with the mean stressor score in the study being 9.6, Ms. Dommershuijsen said.
The BDI and STAI scores for social stressors – loss of social contacts, social events canceled and tension or conflict at home – exceeded those for the so-called care stressors – problems accessing care, medication or nursing – she said, although all eight stressors yielded higher BDI and STAI scores across the board.
Vulnerable subgroups
“When we looked at vulnerable subgroups of people with Parkinson’s disease, we found more pronounced associations between the COVID-19 stress and mental health in women, in highly educated participants, and in participants with advanced Parkinson’s disease,” Ms. Dommershuijsen said. The impact on women and people with advanced disease is explainable, Ms. Dommershuijsen added in an interview; the former because depressive symptoms are more common in women, and the latter because loss of access to care impacts mental wellness.
“The finding that social stressors were more related to anxiety in highly educated people was surprising to us, given that depression in general is more common in people with a lower education,” she said in an interview. “One previous study of the general population suggested this might be related to expectations about available resources, but this findings and the possible explanation warrants further investigation.”
When the study stratified for coping strategies, the COVID-19 stressors had a smaller effect on depressive and anxiety symptoms in Parkinson’s disease patients prone to confrontive coping and planful problem solving, she said. “Whereas, we observed a larger effect of these stressors in people who are prone to using distancing or seeking social support as coping mechanisms,” Ms. Dommershuijsen said.
The researchers also created a model of a hypothetical 50% reduction in COVID-19 stressors among all study participants, but the effect wasn’t clinically relevant, Ms. Dommershuijsen said. However, in people with advanced Parkinson’s disease – that is, with an Movement Disorder Society–Unified Parkinson Disease Rating Scale score above median – the effect was clinically relevant in all outcomes.
The potential interventions the study identified were telemedicine via virtual consultations to alleviate care stressors, and virtual support groups and online classes to address social stressors. “However, a more personalized approach is needed to target tension or conflict at home, which was the most important social stressor influencing depression and anxiety symptoms in our study,” she said. “Social work can play an important role here.”
Asked to comment on the study, Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, said in an interview that the findings align with his research on the impact of COVID-19 and related restrictions on people with Parkinson’s disease.
“The pandemic has affected people in different ways,” he said. “Initially very acutely, people just didn’t have access to doctors. There was also the acute question in movement disorders, but also in other diseases where the people with Parkinson’s disease are going to have the worse outcome when they have COVID-19.” Dr. Alcalay authored two recent papers on the impact of COVID-19 in people with Parkinson’s disease.
“Then we see that, in addition to that question, there’s the question of even if they don’t have COVID-19, just the social distancing and the lack of access to health care, and specifically to physical and occupational therapy and other services, can be quite damaging,” he said.
What’s commendable about the study, he said, was that it just doesn’t highlight the problem. “They’re also highlighting potential solutions, that planful problem solving and coping strategies can be helpful to people.”
Neither Ms. Dommershuijsen nor Dr. Alcalay have any relevant relationships to disclose.
FROM MDS VIRTUAL CONGRESS 2021
Investigative botulinum toxin formulation shows prolonged effect
, according to results of a phase 3 clinical trial presented at the virtual International Congress of Parkinson’s Disease and Movement Disorders.
The ASPEN-1 trial evaluated 301 patients with moderate to severe cervical dystonia for up to 36 weeks and found that those receiving two doses of DaxibotulinumtoxinA, known as DAXI, versus placebo improved their scores on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), said Joseph Jankovic, MD, professor of neurology and director of the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine in Houston.
“Botulinum neurotoxin is clearly the treatment of choice for cervical dystonia,” Dr. Jankovic said in an interview. “While the majority of patients obtain satisfactory benefit from BoNT injections, some experience adverse effects such as neck weakness and difficulty swallowing.” Another limitation of BoNT is that its effects wear off after about 3 months or less and patients have to be re-injected, he said.
“This is why I am quite encouraged by the results of the DAXI study that suggest that this formulation of BoNT (type A) may have a longer response and relatively few side effects,” he said.
Patients in the study were randomized 1:3:3 to placebo, DAXI 125U or DAXI 250U. The average TWSTRS score upon enrollment was 43.3. The placebo group had a mean ± standard error TWSTRS improvement of 4.3 ± 1.8 at 4 or 6 weeks, while the treatment groups had mean ± SE improvements of 12.7 ± 1.3 for 125U and 10.9 ± 1.2 for 250U (P = .0006 vs. placebo). They translate into improvements of 12%, 31%, and 27% for the placebo and low- and high-dose treatment groups, respectively.
“Even though paradoxically it seems the high-dose group did slightly less well than the low-dose group, there was no difference between the two groups,” Dr. Jankovic said in the presentation.
The median duration of benefit was 24 weeks in the low-dose group and 20.3 weeks in the high-dose group.
The treatment groups demonstrated similar benefit compared with placebo in TWSTRS subscales for disease severity, disability, and pain, Dr. Jankovic said. “The majority of the patients had little better, moderately better, or very much better from the botulinum toxin injection with respect to clinical global impression of change and patient global impression of change,” he said.
Likewise, both the Clinician Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) demonstrated improvement versus placebo: 77.6% and 76.9% in the 125U and 250U doses versus 45.7% for the former; and 71.2% and 73.1% versus 41.3% for the latter.
Side effects “were remarkably minimal,” Dr. Jankovic said, “but I want to call attention to the low frequency of neck weakness or dysphagia in comparison with other studies of botulinum toxin in cervical dystonia.” The rates of dysphagia were 1.6% and 3.9% in the 125U and 250U treatment groups, respectively. Sixteen of the 255 patients in the treatment groups reported muscular weakness or musculoskeletal pain, and seven had dysphagia.
The rate of dysphagia after injection is noteworthy, said David Charles, MD, professor and vice chair of neurology at Vanderbilt University in Nashville, Tenn., who was not involved in the research. “The one thing we worry about most in people with cervical dystonia are swallowing and choking – dysphagia – and the numbers are very modest: 2 out of 127 in the 125U dose and 5 of 130 in the 250U dose,” he said. “That’s a very low rate of that adverse event.”
The duration of action for both doses is “rather remarkable,” Dr. Charles said. “With the other formulations, my patients are coming back every 12 weeks for treatment; the BoNT helps so much that [these] patients make their appointments every 3 months for as far out as they can,” he said. “This could potentially mean two or three trips a year as opposed to four trips a year.”
The trial was funded by Revance Therapeutics. Dr. Jankovic is an investigator for Revance, and three coauthors are employees of Revance. Dr. Charles is a consultant to the company.
, according to results of a phase 3 clinical trial presented at the virtual International Congress of Parkinson’s Disease and Movement Disorders.
The ASPEN-1 trial evaluated 301 patients with moderate to severe cervical dystonia for up to 36 weeks and found that those receiving two doses of DaxibotulinumtoxinA, known as DAXI, versus placebo improved their scores on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), said Joseph Jankovic, MD, professor of neurology and director of the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine in Houston.
“Botulinum neurotoxin is clearly the treatment of choice for cervical dystonia,” Dr. Jankovic said in an interview. “While the majority of patients obtain satisfactory benefit from BoNT injections, some experience adverse effects such as neck weakness and difficulty swallowing.” Another limitation of BoNT is that its effects wear off after about 3 months or less and patients have to be re-injected, he said.
“This is why I am quite encouraged by the results of the DAXI study that suggest that this formulation of BoNT (type A) may have a longer response and relatively few side effects,” he said.
Patients in the study were randomized 1:3:3 to placebo, DAXI 125U or DAXI 250U. The average TWSTRS score upon enrollment was 43.3. The placebo group had a mean ± standard error TWSTRS improvement of 4.3 ± 1.8 at 4 or 6 weeks, while the treatment groups had mean ± SE improvements of 12.7 ± 1.3 for 125U and 10.9 ± 1.2 for 250U (P = .0006 vs. placebo). They translate into improvements of 12%, 31%, and 27% for the placebo and low- and high-dose treatment groups, respectively.
“Even though paradoxically it seems the high-dose group did slightly less well than the low-dose group, there was no difference between the two groups,” Dr. Jankovic said in the presentation.
The median duration of benefit was 24 weeks in the low-dose group and 20.3 weeks in the high-dose group.
The treatment groups demonstrated similar benefit compared with placebo in TWSTRS subscales for disease severity, disability, and pain, Dr. Jankovic said. “The majority of the patients had little better, moderately better, or very much better from the botulinum toxin injection with respect to clinical global impression of change and patient global impression of change,” he said.
Likewise, both the Clinician Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) demonstrated improvement versus placebo: 77.6% and 76.9% in the 125U and 250U doses versus 45.7% for the former; and 71.2% and 73.1% versus 41.3% for the latter.
Side effects “were remarkably minimal,” Dr. Jankovic said, “but I want to call attention to the low frequency of neck weakness or dysphagia in comparison with other studies of botulinum toxin in cervical dystonia.” The rates of dysphagia were 1.6% and 3.9% in the 125U and 250U treatment groups, respectively. Sixteen of the 255 patients in the treatment groups reported muscular weakness or musculoskeletal pain, and seven had dysphagia.
The rate of dysphagia after injection is noteworthy, said David Charles, MD, professor and vice chair of neurology at Vanderbilt University in Nashville, Tenn., who was not involved in the research. “The one thing we worry about most in people with cervical dystonia are swallowing and choking – dysphagia – and the numbers are very modest: 2 out of 127 in the 125U dose and 5 of 130 in the 250U dose,” he said. “That’s a very low rate of that adverse event.”
The duration of action for both doses is “rather remarkable,” Dr. Charles said. “With the other formulations, my patients are coming back every 12 weeks for treatment; the BoNT helps so much that [these] patients make their appointments every 3 months for as far out as they can,” he said. “This could potentially mean two or three trips a year as opposed to four trips a year.”
The trial was funded by Revance Therapeutics. Dr. Jankovic is an investigator for Revance, and three coauthors are employees of Revance. Dr. Charles is a consultant to the company.
, according to results of a phase 3 clinical trial presented at the virtual International Congress of Parkinson’s Disease and Movement Disorders.
The ASPEN-1 trial evaluated 301 patients with moderate to severe cervical dystonia for up to 36 weeks and found that those receiving two doses of DaxibotulinumtoxinA, known as DAXI, versus placebo improved their scores on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), said Joseph Jankovic, MD, professor of neurology and director of the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine in Houston.
“Botulinum neurotoxin is clearly the treatment of choice for cervical dystonia,” Dr. Jankovic said in an interview. “While the majority of patients obtain satisfactory benefit from BoNT injections, some experience adverse effects such as neck weakness and difficulty swallowing.” Another limitation of BoNT is that its effects wear off after about 3 months or less and patients have to be re-injected, he said.
“This is why I am quite encouraged by the results of the DAXI study that suggest that this formulation of BoNT (type A) may have a longer response and relatively few side effects,” he said.
Patients in the study were randomized 1:3:3 to placebo, DAXI 125U or DAXI 250U. The average TWSTRS score upon enrollment was 43.3. The placebo group had a mean ± standard error TWSTRS improvement of 4.3 ± 1.8 at 4 or 6 weeks, while the treatment groups had mean ± SE improvements of 12.7 ± 1.3 for 125U and 10.9 ± 1.2 for 250U (P = .0006 vs. placebo). They translate into improvements of 12%, 31%, and 27% for the placebo and low- and high-dose treatment groups, respectively.
“Even though paradoxically it seems the high-dose group did slightly less well than the low-dose group, there was no difference between the two groups,” Dr. Jankovic said in the presentation.
The median duration of benefit was 24 weeks in the low-dose group and 20.3 weeks in the high-dose group.
The treatment groups demonstrated similar benefit compared with placebo in TWSTRS subscales for disease severity, disability, and pain, Dr. Jankovic said. “The majority of the patients had little better, moderately better, or very much better from the botulinum toxin injection with respect to clinical global impression of change and patient global impression of change,” he said.
Likewise, both the Clinician Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) demonstrated improvement versus placebo: 77.6% and 76.9% in the 125U and 250U doses versus 45.7% for the former; and 71.2% and 73.1% versus 41.3% for the latter.
Side effects “were remarkably minimal,” Dr. Jankovic said, “but I want to call attention to the low frequency of neck weakness or dysphagia in comparison with other studies of botulinum toxin in cervical dystonia.” The rates of dysphagia were 1.6% and 3.9% in the 125U and 250U treatment groups, respectively. Sixteen of the 255 patients in the treatment groups reported muscular weakness or musculoskeletal pain, and seven had dysphagia.
The rate of dysphagia after injection is noteworthy, said David Charles, MD, professor and vice chair of neurology at Vanderbilt University in Nashville, Tenn., who was not involved in the research. “The one thing we worry about most in people with cervical dystonia are swallowing and choking – dysphagia – and the numbers are very modest: 2 out of 127 in the 125U dose and 5 of 130 in the 250U dose,” he said. “That’s a very low rate of that adverse event.”
The duration of action for both doses is “rather remarkable,” Dr. Charles said. “With the other formulations, my patients are coming back every 12 weeks for treatment; the BoNT helps so much that [these] patients make their appointments every 3 months for as far out as they can,” he said. “This could potentially mean two or three trips a year as opposed to four trips a year.”
The trial was funded by Revance Therapeutics. Dr. Jankovic is an investigator for Revance, and three coauthors are employees of Revance. Dr. Charles is a consultant to the company.
FROM MDS VIRTUAL CONGRESS 2021
Efforts target underrepresented populations in Parkinson’s disease genetic studies
, attendees at the International Congress of Parkinson’s Disease and Movement Disorders were told.
“Through the years, as we’ve increased the number of individuals that we’ve included in our genetic studies, the number of risk factors that we’ve been able to identify has increased exponentially,” said Ignacio F. Mata, PhD, a neurogeneticist and principal investigator with the Genomic Medicine Institute of the Cleveland Clinic Lerner Research Institute. “This is all due to collaborations.”
Dr. Mata reviewed no fewer than seven initiatives that are gathering genetic data from people with Parkinson’s disease in Central and South America, India, China, Africa, Oceania, the Middle East, and Central Asia, along with efforts to target diverse populations in London and African Americans in the United States.
“One of the problems that we’ve had in the past is that most of the studies have been done just with individuals that are of European ancestry, so there’s a big gap of other populations that we haven’t been able to study,” Dr. Mata said. “And this is true for all of the current studies that are ongoing here in the United States.” That includes the Parkinson’s Progression Markers Initiative, he said, in which fewer than 6% of participants are non-European. Dr. Mata is also the lead in the Global Parkinson’s Genetics Program (GP2) for underrepresented populations.
Lack of diversity in genetic studies isn’t an issue in Parkinson’s studies alone, Dr. Mata said. “This is a generalized problem across all genetic studies,” he said, citing a 2016 analysis that found the proportion of participants in genome-wide studies was 96% European descent in 2009, shifting to 80% by 2016. “There’s still a big gap because most of the non-European populations came mostly from Asia,” Dr. Mata said, with Latinos and people of African descent representing less than 1% of the study populations.
In an interview, Dr. Mata noted there are a multitude of reasons for enrolling more diverse populations. “We’re going to be able to use genetics to create new treatments and do risk prediction – the so-called precision or personalized medicine,” he said. “We’re leaving a big chunk of the population behind if we don’t include those individuals.”
Scientific basis for diversity
There are a multitude of scientific reasons for doing so, too, said Dr. Mata. “In the whole genome we try to find gene variants that modify the risk for certain disease,” he said. “These regions can be quite large, so increasing the number of individuals that come from different genetic backgrounds can actually help us reduce the number of regions that need to be studied to find the causal variants.”
Andrew Singleton, PhD, director of the Center for Alzheimer’s and Related Dementias at the National Institute of Aging in Bethesda, Md., concurred that enrolling more diverse populations can speed up research for targeting genetic variants.
“We can use the differences in genetics to narrow down our search for variants, reduce the places where we’re looking for risk variants, and reduce the number of genes we’re looking at,” he said in an interview.
Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, offered two more scientific reasons for more diverse study populations “in addition to being more ethically appropriate,” he said. “One is, you may identify new genes that you wouldn’t have identified otherwise; and also in the genes that already exist, you may recognize that some of the pathogenic variants may be more prevalent in populations that were unknown.”
One of the challenges in casting a wider net is that much of the research funding has been concentrated in the United States and Europe, Dr. Mata said. And even in the United States, with large, diverse populations, minority groups are underrepresented in these studies, he said, but a potential solution is emerging. “This is something that we’re learning now with COVID,” he said. “We can do a lot remotely. This should help bring some of those barriers down.”
Cultural barriers are also foreboding. “Individuals may not feel comfortable participating in research,” he said in the interview. “I see this especially in the Hispanic community; many don’t understand what they can do with genetic material, or they’re afraid it will be shared with police, and if they’re here in nonofficial immigration status, they’re afraid they could be deported. There are a lot of misconceptions about genetic research.”
An initiative of the Parkinson’s Foundation PD GENEration Study is to provide free genetic tests and give the patient a report on genetic counseling “to empower patients,” Dr. Mata said.
Solutions for targeting underrepresented groups are emerging, Dr. Singleton said. “Actually there’s a really elegant solution, which is that in the populations that we go into and work with, we make sure the ownership of those cohorts, the ownership of the science and the analysis belongs to those populations,” he said.
“Part of that is creating infrastructure on site,” Dr. Singleton added. “Another part is providing training and outreach so we can help to train a whole new generation of scientists and researchers who can work in those populations embedded within those populations. They’re really the champion of moving that research forward.”
Dr. Alcalay credited Dr. Mata for his work with cohorts in Central and South America and in reaching out to other countries to recruit more diverse populations for genetic Parkinson’s studies. “And it’s not just because it’s the politically correct thing to do, about inclusivity and diversity,” Dr. Alcalay said. “It’s because it’s really meaningful. In addition to being ethically more appropriate, it will advance the entire field.
“I also really think it’s a no-brainer,” Dr. Alcalay said. “It’s something that needs to happen.”
Dr. Mata receives grant funding from the National Institutes of Health. Dr. Singleton and Dr. Alcalay have no relevant disclosures.
, attendees at the International Congress of Parkinson’s Disease and Movement Disorders were told.
“Through the years, as we’ve increased the number of individuals that we’ve included in our genetic studies, the number of risk factors that we’ve been able to identify has increased exponentially,” said Ignacio F. Mata, PhD, a neurogeneticist and principal investigator with the Genomic Medicine Institute of the Cleveland Clinic Lerner Research Institute. “This is all due to collaborations.”
Dr. Mata reviewed no fewer than seven initiatives that are gathering genetic data from people with Parkinson’s disease in Central and South America, India, China, Africa, Oceania, the Middle East, and Central Asia, along with efforts to target diverse populations in London and African Americans in the United States.
“One of the problems that we’ve had in the past is that most of the studies have been done just with individuals that are of European ancestry, so there’s a big gap of other populations that we haven’t been able to study,” Dr. Mata said. “And this is true for all of the current studies that are ongoing here in the United States.” That includes the Parkinson’s Progression Markers Initiative, he said, in which fewer than 6% of participants are non-European. Dr. Mata is also the lead in the Global Parkinson’s Genetics Program (GP2) for underrepresented populations.
Lack of diversity in genetic studies isn’t an issue in Parkinson’s studies alone, Dr. Mata said. “This is a generalized problem across all genetic studies,” he said, citing a 2016 analysis that found the proportion of participants in genome-wide studies was 96% European descent in 2009, shifting to 80% by 2016. “There’s still a big gap because most of the non-European populations came mostly from Asia,” Dr. Mata said, with Latinos and people of African descent representing less than 1% of the study populations.
In an interview, Dr. Mata noted there are a multitude of reasons for enrolling more diverse populations. “We’re going to be able to use genetics to create new treatments and do risk prediction – the so-called precision or personalized medicine,” he said. “We’re leaving a big chunk of the population behind if we don’t include those individuals.”
Scientific basis for diversity
There are a multitude of scientific reasons for doing so, too, said Dr. Mata. “In the whole genome we try to find gene variants that modify the risk for certain disease,” he said. “These regions can be quite large, so increasing the number of individuals that come from different genetic backgrounds can actually help us reduce the number of regions that need to be studied to find the causal variants.”
Andrew Singleton, PhD, director of the Center for Alzheimer’s and Related Dementias at the National Institute of Aging in Bethesda, Md., concurred that enrolling more diverse populations can speed up research for targeting genetic variants.
“We can use the differences in genetics to narrow down our search for variants, reduce the places where we’re looking for risk variants, and reduce the number of genes we’re looking at,” he said in an interview.
Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, offered two more scientific reasons for more diverse study populations “in addition to being more ethically appropriate,” he said. “One is, you may identify new genes that you wouldn’t have identified otherwise; and also in the genes that already exist, you may recognize that some of the pathogenic variants may be more prevalent in populations that were unknown.”
One of the challenges in casting a wider net is that much of the research funding has been concentrated in the United States and Europe, Dr. Mata said. And even in the United States, with large, diverse populations, minority groups are underrepresented in these studies, he said, but a potential solution is emerging. “This is something that we’re learning now with COVID,” he said. “We can do a lot remotely. This should help bring some of those barriers down.”
Cultural barriers are also foreboding. “Individuals may not feel comfortable participating in research,” he said in the interview. “I see this especially in the Hispanic community; many don’t understand what they can do with genetic material, or they’re afraid it will be shared with police, and if they’re here in nonofficial immigration status, they’re afraid they could be deported. There are a lot of misconceptions about genetic research.”
An initiative of the Parkinson’s Foundation PD GENEration Study is to provide free genetic tests and give the patient a report on genetic counseling “to empower patients,” Dr. Mata said.
Solutions for targeting underrepresented groups are emerging, Dr. Singleton said. “Actually there’s a really elegant solution, which is that in the populations that we go into and work with, we make sure the ownership of those cohorts, the ownership of the science and the analysis belongs to those populations,” he said.
“Part of that is creating infrastructure on site,” Dr. Singleton added. “Another part is providing training and outreach so we can help to train a whole new generation of scientists and researchers who can work in those populations embedded within those populations. They’re really the champion of moving that research forward.”
Dr. Alcalay credited Dr. Mata for his work with cohorts in Central and South America and in reaching out to other countries to recruit more diverse populations for genetic Parkinson’s studies. “And it’s not just because it’s the politically correct thing to do, about inclusivity and diversity,” Dr. Alcalay said. “It’s because it’s really meaningful. In addition to being ethically more appropriate, it will advance the entire field.
“I also really think it’s a no-brainer,” Dr. Alcalay said. “It’s something that needs to happen.”
Dr. Mata receives grant funding from the National Institutes of Health. Dr. Singleton and Dr. Alcalay have no relevant disclosures.
, attendees at the International Congress of Parkinson’s Disease and Movement Disorders were told.
“Through the years, as we’ve increased the number of individuals that we’ve included in our genetic studies, the number of risk factors that we’ve been able to identify has increased exponentially,” said Ignacio F. Mata, PhD, a neurogeneticist and principal investigator with the Genomic Medicine Institute of the Cleveland Clinic Lerner Research Institute. “This is all due to collaborations.”
Dr. Mata reviewed no fewer than seven initiatives that are gathering genetic data from people with Parkinson’s disease in Central and South America, India, China, Africa, Oceania, the Middle East, and Central Asia, along with efforts to target diverse populations in London and African Americans in the United States.
“One of the problems that we’ve had in the past is that most of the studies have been done just with individuals that are of European ancestry, so there’s a big gap of other populations that we haven’t been able to study,” Dr. Mata said. “And this is true for all of the current studies that are ongoing here in the United States.” That includes the Parkinson’s Progression Markers Initiative, he said, in which fewer than 6% of participants are non-European. Dr. Mata is also the lead in the Global Parkinson’s Genetics Program (GP2) for underrepresented populations.
Lack of diversity in genetic studies isn’t an issue in Parkinson’s studies alone, Dr. Mata said. “This is a generalized problem across all genetic studies,” he said, citing a 2016 analysis that found the proportion of participants in genome-wide studies was 96% European descent in 2009, shifting to 80% by 2016. “There’s still a big gap because most of the non-European populations came mostly from Asia,” Dr. Mata said, with Latinos and people of African descent representing less than 1% of the study populations.
In an interview, Dr. Mata noted there are a multitude of reasons for enrolling more diverse populations. “We’re going to be able to use genetics to create new treatments and do risk prediction – the so-called precision or personalized medicine,” he said. “We’re leaving a big chunk of the population behind if we don’t include those individuals.”
Scientific basis for diversity
There are a multitude of scientific reasons for doing so, too, said Dr. Mata. “In the whole genome we try to find gene variants that modify the risk for certain disease,” he said. “These regions can be quite large, so increasing the number of individuals that come from different genetic backgrounds can actually help us reduce the number of regions that need to be studied to find the causal variants.”
Andrew Singleton, PhD, director of the Center for Alzheimer’s and Related Dementias at the National Institute of Aging in Bethesda, Md., concurred that enrolling more diverse populations can speed up research for targeting genetic variants.
“We can use the differences in genetics to narrow down our search for variants, reduce the places where we’re looking for risk variants, and reduce the number of genes we’re looking at,” he said in an interview.
Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, offered two more scientific reasons for more diverse study populations “in addition to being more ethically appropriate,” he said. “One is, you may identify new genes that you wouldn’t have identified otherwise; and also in the genes that already exist, you may recognize that some of the pathogenic variants may be more prevalent in populations that were unknown.”
One of the challenges in casting a wider net is that much of the research funding has been concentrated in the United States and Europe, Dr. Mata said. And even in the United States, with large, diverse populations, minority groups are underrepresented in these studies, he said, but a potential solution is emerging. “This is something that we’re learning now with COVID,” he said. “We can do a lot remotely. This should help bring some of those barriers down.”
Cultural barriers are also foreboding. “Individuals may not feel comfortable participating in research,” he said in the interview. “I see this especially in the Hispanic community; many don’t understand what they can do with genetic material, or they’re afraid it will be shared with police, and if they’re here in nonofficial immigration status, they’re afraid they could be deported. There are a lot of misconceptions about genetic research.”
An initiative of the Parkinson’s Foundation PD GENEration Study is to provide free genetic tests and give the patient a report on genetic counseling “to empower patients,” Dr. Mata said.
Solutions for targeting underrepresented groups are emerging, Dr. Singleton said. “Actually there’s a really elegant solution, which is that in the populations that we go into and work with, we make sure the ownership of those cohorts, the ownership of the science and the analysis belongs to those populations,” he said.
“Part of that is creating infrastructure on site,” Dr. Singleton added. “Another part is providing training and outreach so we can help to train a whole new generation of scientists and researchers who can work in those populations embedded within those populations. They’re really the champion of moving that research forward.”
Dr. Alcalay credited Dr. Mata for his work with cohorts in Central and South America and in reaching out to other countries to recruit more diverse populations for genetic Parkinson’s studies. “And it’s not just because it’s the politically correct thing to do, about inclusivity and diversity,” Dr. Alcalay said. “It’s because it’s really meaningful. In addition to being ethically more appropriate, it will advance the entire field.
“I also really think it’s a no-brainer,” Dr. Alcalay said. “It’s something that needs to happen.”
Dr. Mata receives grant funding from the National Institutes of Health. Dr. Singleton and Dr. Alcalay have no relevant disclosures.
FROM MDS VIRTUAL CONGRESS 2021
Synthetic triglyceride shows potential in Huntington’s disease
, according to data presented at the International Congress of Parkinson’s Disease and Movement Disorders.
Reporting results of TRIHEP3 and an extension study, Fanny Mochel, MD, PhD, of Sorbonne University in Paris and the Paris Brain Institute, said in an interview that her group is the only one investigating triheptanoin to target caudate atrophy in Huntington’s disease. The Food and Drug Administration last year approved triheptanoin for the treatment of long-chain fatty acid oxidation disorders.
“The main findings are two observations: that patients were clinically stable based on their gradation of total motor score (TMS) on UHDRS (Unified Huntington’s Disease Rating Scale) after 1 year,” Dr. Mochel said in an interview. “The other is that we observed a reduction of the caudate atrophy progression that we usually see over 1 year by about 50%.”
TRIHEP3 randomized 100 patients with early-stage Huntington’s disease to triheptanoin 1g/kg daily and placebo. It followed on previous research in which the group used 31-phosphorus brain MR spectroscopy to demonstrate triheptanoin restored a normal brain energetic profile in patients with Huntington’s disease. TRIHEP3 was a 6-month randomized controlled trial at two centers, followed by a 6-month open-label phase. After that, 42 patients opted to participate in the 1-year extension study.
TRIHEP3 found no difference in caudate boundary shift integral (cBSI) at 6 months – the primary endpoint. But in the extension study, TMS tended to stabilize in patients treated for 1 year (0.6 ± 5.1), compared with those treated for 6 months (2.5 ± 4.5, P = .072).
Using a placebo control group from an external study of patients with Huntington’s disease with what Dr. Mochel described as “identical clinical characteristics,” she said the research confirmed TMS clinical stability in treated patients at 1 year (2.6 ± 4.6 vs. 0.6 ± 5.1, P = .057) and found significantly lower caudate atrophy (–3% vs. –6.7%, compared with baseline, P < .001).
Dr. Mochel also noted that Diffusion Tensor Imaging and Fixed-based analyses (FBA) showed fewer alterations in fiber metrics at 24 months in patients treated from baseline. FBA also showed improved fiber trophicity at 24 months in both groups.
‘The first good news’
Dr. Mochel noted that the Huntington’s disease community had been shaken in the spring by the failure of three trials of gene-targeting therapies for Huntington’s disease. Roche halted a phase 3 study of its antisense oligonucleotide (ASO) tominersen, and Wave Life Sciences scuttled two ASO programs in phase 1/2 trials.
“Triheptanoin is not going to cure Huntington’s disease; it’s a disease with many components, but it does work on the energy aspects and that seems to stabilize patients over the time of observation,” Dr. Mochel said. “That’s the first good news.”
She also noted that side effects were mainly gastrointestinal in nature, and they typically resolved with dietary management.
As a target in Huntington disease, the caudate nucleus is highly desirable, and caudate atrophy has been shown to occur even before the onset of motor symptoms, said N. Ahmad Aziz, MD, PhD, a neurologist and epidemiologist at the German Center for Neurodegenerative Diseases at the University of Bonn (Germany). “In this light, the findings of the trial conducted by Dr. Mochel and colleagues, which suggest that triheptanoin intake may slow down the rate of caudate atrophy in patients with early-stage Huntington’s disease, are highly promising,” Dr. Aziz said in an interview.
However, he noted that the improvement in caudate atrophy was only a secondary endpoint in the extension study. “Nevertheless, given triheptanoin’s biologically plausible mechanism of action – i.e., provision of substrates to the Krebs cycle and at least partial restoration of the well-documented defective mitochondrial function in Huntington’s disease – combined with its apparently relatively mild side-effect profile and good tolerability, I think that the preliminary findings of this trial are very promising and justify a larger phase 3 trial,” Dr. Aziz said.
Dr. Mochel said that the findings are prompting the investigators to consider just that.
Dr. Mochel has received consulting fees from and conducted investigator‐sponsored studies supported by Ultragenyx Pharmaceuticals. Dr. Aziz has no relevant financial relationships to disclose.
, according to data presented at the International Congress of Parkinson’s Disease and Movement Disorders.
Reporting results of TRIHEP3 and an extension study, Fanny Mochel, MD, PhD, of Sorbonne University in Paris and the Paris Brain Institute, said in an interview that her group is the only one investigating triheptanoin to target caudate atrophy in Huntington’s disease. The Food and Drug Administration last year approved triheptanoin for the treatment of long-chain fatty acid oxidation disorders.
“The main findings are two observations: that patients were clinically stable based on their gradation of total motor score (TMS) on UHDRS (Unified Huntington’s Disease Rating Scale) after 1 year,” Dr. Mochel said in an interview. “The other is that we observed a reduction of the caudate atrophy progression that we usually see over 1 year by about 50%.”
TRIHEP3 randomized 100 patients with early-stage Huntington’s disease to triheptanoin 1g/kg daily and placebo. It followed on previous research in which the group used 31-phosphorus brain MR spectroscopy to demonstrate triheptanoin restored a normal brain energetic profile in patients with Huntington’s disease. TRIHEP3 was a 6-month randomized controlled trial at two centers, followed by a 6-month open-label phase. After that, 42 patients opted to participate in the 1-year extension study.
TRIHEP3 found no difference in caudate boundary shift integral (cBSI) at 6 months – the primary endpoint. But in the extension study, TMS tended to stabilize in patients treated for 1 year (0.6 ± 5.1), compared with those treated for 6 months (2.5 ± 4.5, P = .072).
Using a placebo control group from an external study of patients with Huntington’s disease with what Dr. Mochel described as “identical clinical characteristics,” she said the research confirmed TMS clinical stability in treated patients at 1 year (2.6 ± 4.6 vs. 0.6 ± 5.1, P = .057) and found significantly lower caudate atrophy (–3% vs. –6.7%, compared with baseline, P < .001).
Dr. Mochel also noted that Diffusion Tensor Imaging and Fixed-based analyses (FBA) showed fewer alterations in fiber metrics at 24 months in patients treated from baseline. FBA also showed improved fiber trophicity at 24 months in both groups.
‘The first good news’
Dr. Mochel noted that the Huntington’s disease community had been shaken in the spring by the failure of three trials of gene-targeting therapies for Huntington’s disease. Roche halted a phase 3 study of its antisense oligonucleotide (ASO) tominersen, and Wave Life Sciences scuttled two ASO programs in phase 1/2 trials.
“Triheptanoin is not going to cure Huntington’s disease; it’s a disease with many components, but it does work on the energy aspects and that seems to stabilize patients over the time of observation,” Dr. Mochel said. “That’s the first good news.”
She also noted that side effects were mainly gastrointestinal in nature, and they typically resolved with dietary management.
As a target in Huntington disease, the caudate nucleus is highly desirable, and caudate atrophy has been shown to occur even before the onset of motor symptoms, said N. Ahmad Aziz, MD, PhD, a neurologist and epidemiologist at the German Center for Neurodegenerative Diseases at the University of Bonn (Germany). “In this light, the findings of the trial conducted by Dr. Mochel and colleagues, which suggest that triheptanoin intake may slow down the rate of caudate atrophy in patients with early-stage Huntington’s disease, are highly promising,” Dr. Aziz said in an interview.
However, he noted that the improvement in caudate atrophy was only a secondary endpoint in the extension study. “Nevertheless, given triheptanoin’s biologically plausible mechanism of action – i.e., provision of substrates to the Krebs cycle and at least partial restoration of the well-documented defective mitochondrial function in Huntington’s disease – combined with its apparently relatively mild side-effect profile and good tolerability, I think that the preliminary findings of this trial are very promising and justify a larger phase 3 trial,” Dr. Aziz said.
Dr. Mochel said that the findings are prompting the investigators to consider just that.
Dr. Mochel has received consulting fees from and conducted investigator‐sponsored studies supported by Ultragenyx Pharmaceuticals. Dr. Aziz has no relevant financial relationships to disclose.
, according to data presented at the International Congress of Parkinson’s Disease and Movement Disorders.
Reporting results of TRIHEP3 and an extension study, Fanny Mochel, MD, PhD, of Sorbonne University in Paris and the Paris Brain Institute, said in an interview that her group is the only one investigating triheptanoin to target caudate atrophy in Huntington’s disease. The Food and Drug Administration last year approved triheptanoin for the treatment of long-chain fatty acid oxidation disorders.
“The main findings are two observations: that patients were clinically stable based on their gradation of total motor score (TMS) on UHDRS (Unified Huntington’s Disease Rating Scale) after 1 year,” Dr. Mochel said in an interview. “The other is that we observed a reduction of the caudate atrophy progression that we usually see over 1 year by about 50%.”
TRIHEP3 randomized 100 patients with early-stage Huntington’s disease to triheptanoin 1g/kg daily and placebo. It followed on previous research in which the group used 31-phosphorus brain MR spectroscopy to demonstrate triheptanoin restored a normal brain energetic profile in patients with Huntington’s disease. TRIHEP3 was a 6-month randomized controlled trial at two centers, followed by a 6-month open-label phase. After that, 42 patients opted to participate in the 1-year extension study.
TRIHEP3 found no difference in caudate boundary shift integral (cBSI) at 6 months – the primary endpoint. But in the extension study, TMS tended to stabilize in patients treated for 1 year (0.6 ± 5.1), compared with those treated for 6 months (2.5 ± 4.5, P = .072).
Using a placebo control group from an external study of patients with Huntington’s disease with what Dr. Mochel described as “identical clinical characteristics,” she said the research confirmed TMS clinical stability in treated patients at 1 year (2.6 ± 4.6 vs. 0.6 ± 5.1, P = .057) and found significantly lower caudate atrophy (–3% vs. –6.7%, compared with baseline, P < .001).
Dr. Mochel also noted that Diffusion Tensor Imaging and Fixed-based analyses (FBA) showed fewer alterations in fiber metrics at 24 months in patients treated from baseline. FBA also showed improved fiber trophicity at 24 months in both groups.
‘The first good news’
Dr. Mochel noted that the Huntington’s disease community had been shaken in the spring by the failure of three trials of gene-targeting therapies for Huntington’s disease. Roche halted a phase 3 study of its antisense oligonucleotide (ASO) tominersen, and Wave Life Sciences scuttled two ASO programs in phase 1/2 trials.
“Triheptanoin is not going to cure Huntington’s disease; it’s a disease with many components, but it does work on the energy aspects and that seems to stabilize patients over the time of observation,” Dr. Mochel said. “That’s the first good news.”
She also noted that side effects were mainly gastrointestinal in nature, and they typically resolved with dietary management.
As a target in Huntington disease, the caudate nucleus is highly desirable, and caudate atrophy has been shown to occur even before the onset of motor symptoms, said N. Ahmad Aziz, MD, PhD, a neurologist and epidemiologist at the German Center for Neurodegenerative Diseases at the University of Bonn (Germany). “In this light, the findings of the trial conducted by Dr. Mochel and colleagues, which suggest that triheptanoin intake may slow down the rate of caudate atrophy in patients with early-stage Huntington’s disease, are highly promising,” Dr. Aziz said in an interview.
However, he noted that the improvement in caudate atrophy was only a secondary endpoint in the extension study. “Nevertheless, given triheptanoin’s biologically plausible mechanism of action – i.e., provision of substrates to the Krebs cycle and at least partial restoration of the well-documented defective mitochondrial function in Huntington’s disease – combined with its apparently relatively mild side-effect profile and good tolerability, I think that the preliminary findings of this trial are very promising and justify a larger phase 3 trial,” Dr. Aziz said.
Dr. Mochel said that the findings are prompting the investigators to consider just that.
Dr. Mochel has received consulting fees from and conducted investigator‐sponsored studies supported by Ultragenyx Pharmaceuticals. Dr. Aziz has no relevant financial relationships to disclose.
FROM MDS VIRTUAL CONGRESS 2021
RA treatment responders show unique differences in gut microbiome
The gut microbiome, previously shown to have an association with rheumatoid arthritis, may also provide signals of a patient’s disease prognosis, researchers at the Mayo Clinic have reported.
“We found that the gut microbiome is linked to whether patients with RA improve in their clinical symptoms or not,” cosenior author Jaeyun Sung, PhD, said in an interview. “We found features of the gut microbiome that linked to improvement, and we also put those features in a machine-learning model that can actually predict improvement at a follow-up visit.” Dr. Sung is a computational biologist with Mayo Clinic’s Center for Individualized Medicine in Rochester, Minn.
The retrospective, observational cohort study included 32 patients diagnosed with RA between 1988 and 2014. The researchers performed meta-genome shotgun sequencing on 64 stool samples kept in a biobank and collected at two separate visits 6-12 months apart. Dr. Sung and colleagues observed significantly different microbiome traits between patients who eventually showed minimally clinically important improvement and those who didn’t.
The study also provided a proof of concept for using machine-learning technology to analyze the gut microbiome to predict the course of the disease, Dr. Sung said.
Cosenior author John M. Davis III, MD, a clinical rheumatologist and rheumatology research chair of the Mayo Clinic, noted that their own previous study had confirmed dysbiosis in people with RA when compared with controls. “We had some preliminary insight that it may be linked to some extent to the disease state and maybe treatments,” Dr. Davis said. “So that led us to hypothesize that there may be an association between the gut microbiome and response to treatment or disease activity over time.”
The study found that age was the dominant factor in determining variations in the gut microbiome composition, but the next prevailing factor was minimum clinically important improvement status, which 12 of the 32 study participants achieved at their follow-up visits. At baseline, all patients were on some type of treatment – either biologic or conventional disease-modifying antirheumatic drugs (DMARDs, 46.9% and 87.5%, respectively), or prednisone (46.9%).
Gut microbiome composition
The patients who achieved minimum clinically important improvement had an average decline in Clinical Disease Activity Index of 16.7 units (standard deviation, 12.8) versus a gain of 5.7 (SD, 8.9) in the remaining patients. The study found higher species-level alpha diversity and richness and higher beta diversity in the group that achieved minimum clinically important improvement, compared with those who did not.
They identified six microbial taxa as higher in abundance in the improved patients: Negativicutes (class); Selenomonadales (order); Prevotellaceae (family); Coprococcus (genus); Bacteroides sp. 3_1_19 (species); and Bilophila sp. 4_1_30 (species). In the patients who showed no improvement, Eubacterium sp. 3_1_31 (species) was found to be higher (P < .05). They also found 15 metabolic pathways that were differently abundant between the two groups at baseline.
Two things make this study different from other studies of the gut microbiome in RA, Dr. Sung said: It didn’t have a control group, only RA patients, and it didn’t evaluate a specific drug in RA patients.
“We’re thinking beyond just drug or treatment, independent of prior treatment, independent of prior clinical measurements, independent of age, sex, and other factors, can we predict RA response just using the gut microbiome alone?” Dr. Sung said. “Is there an association between clinical improvement and the gut microbiome?”
The study also showed that the microbiome may be a modifiable target for RA, Dr. Davis said.
“This research is attractive because it may complement medical treatment for RA if we can identify dietary modifications,” he said. “Still, there’s the question if probiotics or prebiotics can influence the gut. Can we modify the gut microbiome to further ameliorate the disease state? That’s something I think is an open question that’s specifically called out in our paper.”
This study included patients with long-term disease, but the group’s ongoing research is focusing on patients with earlier-stage RA, Dr. Davis said. “The next steps have to be in validating [the findings] in additional and external populations and looking at patients with very early disease where a lot of the decision-making is very active and happening in real time.”
James T. Rosenbaum, MD, an ophthalmologist and rheumatologist at Oregon Health & Science University, Portland, acknowledged that this is the first study in RA to find an effect on the gut microbiome using the minimum clinically important improvement endpoint.
“It also raises a ‘chicken-egg’ dilemma,” Dr. Rosenbaum said in an interview. “Did the patients improve and then their microbiome changed, or was the microbiome the first change that led to the clinical improvement? If the latter is correct, we potentially could alter the microbiome, for example, by diet, to treat rheumatic disease.”
He noted that studies with fecal transplants for ulcerative colitis support the therapeutic potential of microbiome modification. “But,” he added, “we are still a long way from putting this in practice.”
“The outcome is promising,” Claudia Mauri, PhD, a professor of immunology at University College London, said of the study. “Obviously, if this can be repeated in a very large cohort of patients, it would give us the possibility to be able to, based on the composition of the microbiota, to predict who is going to respond to treatment or not.”
She noted that, while RA has a broader array of available treatments than other autoimmune diseases, some RA patients don’t respond their first biologic treatment. “If from the outset we would be able to see who may not respond based on the microbiota, we may prepare physicians to better target these patients by, for example, offering them an alternative second biologic agent,” Dr. Mauri said.
Dr. Davis reported receiving research grants from Pfizer. Dr. Sung and other study coauthors have no financial relationships to disclose. Dr. Rosenbaum reported that the National Institutes of Health supports his research. Dr. Mauri has no financial relationships to disclose.
The gut microbiome, previously shown to have an association with rheumatoid arthritis, may also provide signals of a patient’s disease prognosis, researchers at the Mayo Clinic have reported.
“We found that the gut microbiome is linked to whether patients with RA improve in their clinical symptoms or not,” cosenior author Jaeyun Sung, PhD, said in an interview. “We found features of the gut microbiome that linked to improvement, and we also put those features in a machine-learning model that can actually predict improvement at a follow-up visit.” Dr. Sung is a computational biologist with Mayo Clinic’s Center for Individualized Medicine in Rochester, Minn.
The retrospective, observational cohort study included 32 patients diagnosed with RA between 1988 and 2014. The researchers performed meta-genome shotgun sequencing on 64 stool samples kept in a biobank and collected at two separate visits 6-12 months apart. Dr. Sung and colleagues observed significantly different microbiome traits between patients who eventually showed minimally clinically important improvement and those who didn’t.
The study also provided a proof of concept for using machine-learning technology to analyze the gut microbiome to predict the course of the disease, Dr. Sung said.
Cosenior author John M. Davis III, MD, a clinical rheumatologist and rheumatology research chair of the Mayo Clinic, noted that their own previous study had confirmed dysbiosis in people with RA when compared with controls. “We had some preliminary insight that it may be linked to some extent to the disease state and maybe treatments,” Dr. Davis said. “So that led us to hypothesize that there may be an association between the gut microbiome and response to treatment or disease activity over time.”
The study found that age was the dominant factor in determining variations in the gut microbiome composition, but the next prevailing factor was minimum clinically important improvement status, which 12 of the 32 study participants achieved at their follow-up visits. At baseline, all patients were on some type of treatment – either biologic or conventional disease-modifying antirheumatic drugs (DMARDs, 46.9% and 87.5%, respectively), or prednisone (46.9%).
Gut microbiome composition
The patients who achieved minimum clinically important improvement had an average decline in Clinical Disease Activity Index of 16.7 units (standard deviation, 12.8) versus a gain of 5.7 (SD, 8.9) in the remaining patients. The study found higher species-level alpha diversity and richness and higher beta diversity in the group that achieved minimum clinically important improvement, compared with those who did not.
They identified six microbial taxa as higher in abundance in the improved patients: Negativicutes (class); Selenomonadales (order); Prevotellaceae (family); Coprococcus (genus); Bacteroides sp. 3_1_19 (species); and Bilophila sp. 4_1_30 (species). In the patients who showed no improvement, Eubacterium sp. 3_1_31 (species) was found to be higher (P < .05). They also found 15 metabolic pathways that were differently abundant between the two groups at baseline.
Two things make this study different from other studies of the gut microbiome in RA, Dr. Sung said: It didn’t have a control group, only RA patients, and it didn’t evaluate a specific drug in RA patients.
“We’re thinking beyond just drug or treatment, independent of prior treatment, independent of prior clinical measurements, independent of age, sex, and other factors, can we predict RA response just using the gut microbiome alone?” Dr. Sung said. “Is there an association between clinical improvement and the gut microbiome?”
The study also showed that the microbiome may be a modifiable target for RA, Dr. Davis said.
“This research is attractive because it may complement medical treatment for RA if we can identify dietary modifications,” he said. “Still, there’s the question if probiotics or prebiotics can influence the gut. Can we modify the gut microbiome to further ameliorate the disease state? That’s something I think is an open question that’s specifically called out in our paper.”
This study included patients with long-term disease, but the group’s ongoing research is focusing on patients with earlier-stage RA, Dr. Davis said. “The next steps have to be in validating [the findings] in additional and external populations and looking at patients with very early disease where a lot of the decision-making is very active and happening in real time.”
James T. Rosenbaum, MD, an ophthalmologist and rheumatologist at Oregon Health & Science University, Portland, acknowledged that this is the first study in RA to find an effect on the gut microbiome using the minimum clinically important improvement endpoint.
“It also raises a ‘chicken-egg’ dilemma,” Dr. Rosenbaum said in an interview. “Did the patients improve and then their microbiome changed, or was the microbiome the first change that led to the clinical improvement? If the latter is correct, we potentially could alter the microbiome, for example, by diet, to treat rheumatic disease.”
He noted that studies with fecal transplants for ulcerative colitis support the therapeutic potential of microbiome modification. “But,” he added, “we are still a long way from putting this in practice.”
“The outcome is promising,” Claudia Mauri, PhD, a professor of immunology at University College London, said of the study. “Obviously, if this can be repeated in a very large cohort of patients, it would give us the possibility to be able to, based on the composition of the microbiota, to predict who is going to respond to treatment or not.”
She noted that, while RA has a broader array of available treatments than other autoimmune diseases, some RA patients don’t respond their first biologic treatment. “If from the outset we would be able to see who may not respond based on the microbiota, we may prepare physicians to better target these patients by, for example, offering them an alternative second biologic agent,” Dr. Mauri said.
Dr. Davis reported receiving research grants from Pfizer. Dr. Sung and other study coauthors have no financial relationships to disclose. Dr. Rosenbaum reported that the National Institutes of Health supports his research. Dr. Mauri has no financial relationships to disclose.
The gut microbiome, previously shown to have an association with rheumatoid arthritis, may also provide signals of a patient’s disease prognosis, researchers at the Mayo Clinic have reported.
“We found that the gut microbiome is linked to whether patients with RA improve in their clinical symptoms or not,” cosenior author Jaeyun Sung, PhD, said in an interview. “We found features of the gut microbiome that linked to improvement, and we also put those features in a machine-learning model that can actually predict improvement at a follow-up visit.” Dr. Sung is a computational biologist with Mayo Clinic’s Center for Individualized Medicine in Rochester, Minn.
The retrospective, observational cohort study included 32 patients diagnosed with RA between 1988 and 2014. The researchers performed meta-genome shotgun sequencing on 64 stool samples kept in a biobank and collected at two separate visits 6-12 months apart. Dr. Sung and colleagues observed significantly different microbiome traits between patients who eventually showed minimally clinically important improvement and those who didn’t.
The study also provided a proof of concept for using machine-learning technology to analyze the gut microbiome to predict the course of the disease, Dr. Sung said.
Cosenior author John M. Davis III, MD, a clinical rheumatologist and rheumatology research chair of the Mayo Clinic, noted that their own previous study had confirmed dysbiosis in people with RA when compared with controls. “We had some preliminary insight that it may be linked to some extent to the disease state and maybe treatments,” Dr. Davis said. “So that led us to hypothesize that there may be an association between the gut microbiome and response to treatment or disease activity over time.”
The study found that age was the dominant factor in determining variations in the gut microbiome composition, but the next prevailing factor was minimum clinically important improvement status, which 12 of the 32 study participants achieved at their follow-up visits. At baseline, all patients were on some type of treatment – either biologic or conventional disease-modifying antirheumatic drugs (DMARDs, 46.9% and 87.5%, respectively), or prednisone (46.9%).
Gut microbiome composition
The patients who achieved minimum clinically important improvement had an average decline in Clinical Disease Activity Index of 16.7 units (standard deviation, 12.8) versus a gain of 5.7 (SD, 8.9) in the remaining patients. The study found higher species-level alpha diversity and richness and higher beta diversity in the group that achieved minimum clinically important improvement, compared with those who did not.
They identified six microbial taxa as higher in abundance in the improved patients: Negativicutes (class); Selenomonadales (order); Prevotellaceae (family); Coprococcus (genus); Bacteroides sp. 3_1_19 (species); and Bilophila sp. 4_1_30 (species). In the patients who showed no improvement, Eubacterium sp. 3_1_31 (species) was found to be higher (P < .05). They also found 15 metabolic pathways that were differently abundant between the two groups at baseline.
Two things make this study different from other studies of the gut microbiome in RA, Dr. Sung said: It didn’t have a control group, only RA patients, and it didn’t evaluate a specific drug in RA patients.
“We’re thinking beyond just drug or treatment, independent of prior treatment, independent of prior clinical measurements, independent of age, sex, and other factors, can we predict RA response just using the gut microbiome alone?” Dr. Sung said. “Is there an association between clinical improvement and the gut microbiome?”
The study also showed that the microbiome may be a modifiable target for RA, Dr. Davis said.
“This research is attractive because it may complement medical treatment for RA if we can identify dietary modifications,” he said. “Still, there’s the question if probiotics or prebiotics can influence the gut. Can we modify the gut microbiome to further ameliorate the disease state? That’s something I think is an open question that’s specifically called out in our paper.”
This study included patients with long-term disease, but the group’s ongoing research is focusing on patients with earlier-stage RA, Dr. Davis said. “The next steps have to be in validating [the findings] in additional and external populations and looking at patients with very early disease where a lot of the decision-making is very active and happening in real time.”
James T. Rosenbaum, MD, an ophthalmologist and rheumatologist at Oregon Health & Science University, Portland, acknowledged that this is the first study in RA to find an effect on the gut microbiome using the minimum clinically important improvement endpoint.
“It also raises a ‘chicken-egg’ dilemma,” Dr. Rosenbaum said in an interview. “Did the patients improve and then their microbiome changed, or was the microbiome the first change that led to the clinical improvement? If the latter is correct, we potentially could alter the microbiome, for example, by diet, to treat rheumatic disease.”
He noted that studies with fecal transplants for ulcerative colitis support the therapeutic potential of microbiome modification. “But,” he added, “we are still a long way from putting this in practice.”
“The outcome is promising,” Claudia Mauri, PhD, a professor of immunology at University College London, said of the study. “Obviously, if this can be repeated in a very large cohort of patients, it would give us the possibility to be able to, based on the composition of the microbiota, to predict who is going to respond to treatment or not.”
She noted that, while RA has a broader array of available treatments than other autoimmune diseases, some RA patients don’t respond their first biologic treatment. “If from the outset we would be able to see who may not respond based on the microbiota, we may prepare physicians to better target these patients by, for example, offering them an alternative second biologic agent,” Dr. Mauri said.
Dr. Davis reported receiving research grants from Pfizer. Dr. Sung and other study coauthors have no financial relationships to disclose. Dr. Rosenbaum reported that the National Institutes of Health supports his research. Dr. Mauri has no financial relationships to disclose.
FROM GENOME MEDICINE
Friedreich’s ataxia treatment shows extended benefit
according to results of a clinical trial presented as a late-breaking abstract at the International Congress of Parkinson’s Disease and Movement Disorders.
The study, labeled the Delayed-Start Study, is an extension study of the two-part MOXIE phase 2 trial of omaveloxolone.
“This study shows two things,” said David Lynch, MD, PhD, of Children’s Hospital of Philadelphia. “It doesn’t matter when you started omaveloxolone for you to see a benefit; and that the benefit that the active group saw in the first part of the study was maintained as they went into the delayed-start part. So in fact omaveloxolone does modify the long-term behavior of the disease.”
Friedreich’s ataxia only affects about 22,000 people worldwide, and children typically present between the ages of 5 and 15, Dr. Lynch said.
The extension study included 73 patients who completed either of the first two parts of the MOXIe trial. The MOXIe trial randomized patients on a 3:1 basis to either omaveloxolone 2.5-300 mg or placebo for 12 weeks in the first part. The second part was a double-blind trial of 103 patients randomized on a 1:1 basis to 150 mg omaveloxolone or placebo for 48 weeks. Participants had a baseline modified Friedreich’s ataxia scale (mFARS) of 20-80 and were aged 16-40 years.
Patients in the extension study did not have severe pes cavus. The extension study was a 72-week evaluation of patients who were in either the treatment or placebo groups in the first two parts. There was a 4-week off-treatment period between the end of MOXIe part 2 and the beginning of the extension study, in which all patients received omaveloxolone.
At the end of the placebo-controlled study, patients taking omaveloxolone showed a –2.18-point (±0.96) difference in improvement in mFARS score (P = .027), compared with the placebo group, which was preserved at the end of the delayed-start period, with a –2.92-point (±2.13) improvement (P = .179), Dr. Lynch said.
In the extension study, former placebo patients who went on omaveloxolone had annualized mFARS slopes similar to the previously treated patients – 0.29 (±0.68) and 0.17 (±0.61), respectively (P = .85) – from weeks 48 to 144, Dr. Lynch said.
“This study showed that, when analyzed in a delayed-start fashion, it does not matter when you start omaveloxolone to see a benefit: Each cohort benefited almost equally once they started the drug,” Dr. Lynch said in an interview. “Also, in both groups, once they started omaveloxolone, they changed slower than people in natural history studies.”
A clinically meaningful difference?
Reached for comment, Massimo Pandolfo, MD, a neurologist at McGill University, Montreal, noted that the Delayed-Start Study included only patients without pes cavus, an indication that the patients had less severe disease. “It would be important to see how overall patients with Friedreich’s ataxia would have responded to the medication without this kind of selection,” Dr. Pandolfo said in an interview.
He also noted that the seemingly modest improvement in mFARS score could be an issue. “It’s a very difficult question: What is a clinically meaningful difference in this kind of rating scale? I would argue that probably 2 points is not a huge difference by itself, but it may be meaningful and one indicator of that is that if it was accompanied by also a significant difference in activities of daily living scale.”
In any event, Dr. Pandolfo said this is the first medication for Friedreich’s ataxia that has “survived” a randomized clinical trial.
Dr. Lynch said the study sponsor, Reata, may prepare a new drug application for omaveloxolone in patients ages 16 and older. “That would leave a need for investigation in younger FA patients.”
Dr. Lynch disclosed that his institution receives a grant from trial sponsor Reata to conduct the MOXIe trial. Dr. Pandolfo reports financial relationships with Design Therapeutics, Exicure and Voyager Therapeutics.
according to results of a clinical trial presented as a late-breaking abstract at the International Congress of Parkinson’s Disease and Movement Disorders.
The study, labeled the Delayed-Start Study, is an extension study of the two-part MOXIE phase 2 trial of omaveloxolone.
“This study shows two things,” said David Lynch, MD, PhD, of Children’s Hospital of Philadelphia. “It doesn’t matter when you started omaveloxolone for you to see a benefit; and that the benefit that the active group saw in the first part of the study was maintained as they went into the delayed-start part. So in fact omaveloxolone does modify the long-term behavior of the disease.”
Friedreich’s ataxia only affects about 22,000 people worldwide, and children typically present between the ages of 5 and 15, Dr. Lynch said.
The extension study included 73 patients who completed either of the first two parts of the MOXIe trial. The MOXIe trial randomized patients on a 3:1 basis to either omaveloxolone 2.5-300 mg or placebo for 12 weeks in the first part. The second part was a double-blind trial of 103 patients randomized on a 1:1 basis to 150 mg omaveloxolone or placebo for 48 weeks. Participants had a baseline modified Friedreich’s ataxia scale (mFARS) of 20-80 and were aged 16-40 years.
Patients in the extension study did not have severe pes cavus. The extension study was a 72-week evaluation of patients who were in either the treatment or placebo groups in the first two parts. There was a 4-week off-treatment period between the end of MOXIe part 2 and the beginning of the extension study, in which all patients received omaveloxolone.
At the end of the placebo-controlled study, patients taking omaveloxolone showed a –2.18-point (±0.96) difference in improvement in mFARS score (P = .027), compared with the placebo group, which was preserved at the end of the delayed-start period, with a –2.92-point (±2.13) improvement (P = .179), Dr. Lynch said.
In the extension study, former placebo patients who went on omaveloxolone had annualized mFARS slopes similar to the previously treated patients – 0.29 (±0.68) and 0.17 (±0.61), respectively (P = .85) – from weeks 48 to 144, Dr. Lynch said.
“This study showed that, when analyzed in a delayed-start fashion, it does not matter when you start omaveloxolone to see a benefit: Each cohort benefited almost equally once they started the drug,” Dr. Lynch said in an interview. “Also, in both groups, once they started omaveloxolone, they changed slower than people in natural history studies.”
A clinically meaningful difference?
Reached for comment, Massimo Pandolfo, MD, a neurologist at McGill University, Montreal, noted that the Delayed-Start Study included only patients without pes cavus, an indication that the patients had less severe disease. “It would be important to see how overall patients with Friedreich’s ataxia would have responded to the medication without this kind of selection,” Dr. Pandolfo said in an interview.
He also noted that the seemingly modest improvement in mFARS score could be an issue. “It’s a very difficult question: What is a clinically meaningful difference in this kind of rating scale? I would argue that probably 2 points is not a huge difference by itself, but it may be meaningful and one indicator of that is that if it was accompanied by also a significant difference in activities of daily living scale.”
In any event, Dr. Pandolfo said this is the first medication for Friedreich’s ataxia that has “survived” a randomized clinical trial.
Dr. Lynch said the study sponsor, Reata, may prepare a new drug application for omaveloxolone in patients ages 16 and older. “That would leave a need for investigation in younger FA patients.”
Dr. Lynch disclosed that his institution receives a grant from trial sponsor Reata to conduct the MOXIe trial. Dr. Pandolfo reports financial relationships with Design Therapeutics, Exicure and Voyager Therapeutics.
according to results of a clinical trial presented as a late-breaking abstract at the International Congress of Parkinson’s Disease and Movement Disorders.
The study, labeled the Delayed-Start Study, is an extension study of the two-part MOXIE phase 2 trial of omaveloxolone.
“This study shows two things,” said David Lynch, MD, PhD, of Children’s Hospital of Philadelphia. “It doesn’t matter when you started omaveloxolone for you to see a benefit; and that the benefit that the active group saw in the first part of the study was maintained as they went into the delayed-start part. So in fact omaveloxolone does modify the long-term behavior of the disease.”
Friedreich’s ataxia only affects about 22,000 people worldwide, and children typically present between the ages of 5 and 15, Dr. Lynch said.
The extension study included 73 patients who completed either of the first two parts of the MOXIe trial. The MOXIe trial randomized patients on a 3:1 basis to either omaveloxolone 2.5-300 mg or placebo for 12 weeks in the first part. The second part was a double-blind trial of 103 patients randomized on a 1:1 basis to 150 mg omaveloxolone or placebo for 48 weeks. Participants had a baseline modified Friedreich’s ataxia scale (mFARS) of 20-80 and were aged 16-40 years.
Patients in the extension study did not have severe pes cavus. The extension study was a 72-week evaluation of patients who were in either the treatment or placebo groups in the first two parts. There was a 4-week off-treatment period between the end of MOXIe part 2 and the beginning of the extension study, in which all patients received omaveloxolone.
At the end of the placebo-controlled study, patients taking omaveloxolone showed a –2.18-point (±0.96) difference in improvement in mFARS score (P = .027), compared with the placebo group, which was preserved at the end of the delayed-start period, with a –2.92-point (±2.13) improvement (P = .179), Dr. Lynch said.
In the extension study, former placebo patients who went on omaveloxolone had annualized mFARS slopes similar to the previously treated patients – 0.29 (±0.68) and 0.17 (±0.61), respectively (P = .85) – from weeks 48 to 144, Dr. Lynch said.
“This study showed that, when analyzed in a delayed-start fashion, it does not matter when you start omaveloxolone to see a benefit: Each cohort benefited almost equally once they started the drug,” Dr. Lynch said in an interview. “Also, in both groups, once they started omaveloxolone, they changed slower than people in natural history studies.”
A clinically meaningful difference?
Reached for comment, Massimo Pandolfo, MD, a neurologist at McGill University, Montreal, noted that the Delayed-Start Study included only patients without pes cavus, an indication that the patients had less severe disease. “It would be important to see how overall patients with Friedreich’s ataxia would have responded to the medication without this kind of selection,” Dr. Pandolfo said in an interview.
He also noted that the seemingly modest improvement in mFARS score could be an issue. “It’s a very difficult question: What is a clinically meaningful difference in this kind of rating scale? I would argue that probably 2 points is not a huge difference by itself, but it may be meaningful and one indicator of that is that if it was accompanied by also a significant difference in activities of daily living scale.”
In any event, Dr. Pandolfo said this is the first medication for Friedreich’s ataxia that has “survived” a randomized clinical trial.
Dr. Lynch said the study sponsor, Reata, may prepare a new drug application for omaveloxolone in patients ages 16 and older. “That would leave a need for investigation in younger FA patients.”
Dr. Lynch disclosed that his institution receives a grant from trial sponsor Reata to conduct the MOXIe trial. Dr. Pandolfo reports financial relationships with Design Therapeutics, Exicure and Voyager Therapeutics.
FROM MDS VIRTUAL CONGRESS 2021
Survey identifies clinicians’ unease with genetic testing
Before getting to work on developing guidelines for genetic testing in Parkinson’s disease, a task force of the Movement Disorders Society surveyed members worldwide to identify concerns they have about using genetic testing in practice. In results presented as a late-breaking abstract at the International Congress of Parkinson’s Disease and Movement Disorders,
“Some of the major outstanding issues are the clinical actionability of genetic testing – and this was highlighted by some survey participants,” senior study author Rachel Saunders-Pullman, MD, MPH, professor of neurology at the Icahn School of Medicine at Mount Sinai, New York, said in an interview. The issue is “dynamic,” and will change even more radically when genetic therapies for Parkinson’s disease become available. “It is planned that, in the development of the MDS Task Force guidelines, scenarios which outline the changes in consideration of testing will depend on the availability of clinically actionable data,” she said.
Barriers to genetic testing
The MDS Task Force for Genetic Testing in Parkinson Disease conducted the survey, completed online by 568 MDS members. Respondents were from the four regions from which the MDS draws members: Africa, Europe, Asia/Oceania, and Pan-America. Half of the respondents considered themselves movement disorder specialists and 31% as general neurologists, said Maggie Markgraf, research coordinator at Mount Sinai Beth Israel in New York, who presented the survey findings.
Barriers to genetic testing that the clinicians cited included cost (57%), lack of availability of genetic counseling (37%), time for testing (20%) or time for counseling (17%). About 14%also cited a lack of knowledge, and only 8.5 % said they saw no barriers for genetic testing. Other concerns included a lack of therapeutic options if tests are positive and low overall positivity rates.
“Perceived barriers for general neurologists differed slightly, with limited knowledge being the most widely reported barrier, followed closely by cost and access to testing and genetic counseling,” Ms. Markgraf said.
Respondents were also asked to identify what they thought their patients perceived as barriers to genetic testing. The major one was cost (65%), followed by limited knowledge about genetics (43%), lack of access to genetic counseling (34%), and lack of access to testing separate from cost (30%). “Across all MDS regions, the perceived level of a patient’s knowledge about genetic testing is considered to be exceedingly low,” Ms. Markgraf said.
Europe had the highest availability to genetic tests, with 41.8% saying they’re accessible to general neurologists, followed by Asia/Oceania (31%) and Pan-America (30%).
“The area of most unmet need when it comes to PD genetic testing was cost for each MDS region, although the intertwined issue of access was also high, and over 50% reported that knowledge was an unmet need in their region,” Dr. Saunders-Pullman said.
Insurance coverage was another issue the survey respondents identified. In Europe, 53.6% said insurance or government programs cover genetic testing for PD, while only 14% in Pan-America and 10.3% in Asia/Oceania (and 0% in Africa) said such coverage was available.
“While there are limitations to this study, greater awareness of availability and barriers to genetic testing and counseling across different regions, as well as disparities among regions, will help inform development of the MDS Task Force guidelines,” Dr. Saunders-Pullman said.
Unmet needs
Connie Marras, MD, PhD, a professor of neurology at the University of Toronto, noted the survey suggested neurologists exhibit a “lack of comfort or lack of time” with genetic testing and counseling for Parkinson’s disease. “Even if we make genetic testing more widely available, we need health care providers that are comfortable and available to counsel patients before and after the testing, and clearly these are unmet needs,” Dr. Marras said in an interview.
“To date, pharmacologic treatment of Parkinson’s disease did not depend on genetics,” Dr. Marras said. “This may well change in the near future with treatments specifically targeting mechanisms related to two of the most common genetic risk factors for PD: LRRK2 and GBA gene variants being in clinical trials.” These developments may soon raise the urgency to reduce barriers to genetic testing.
Dr. Saunders-Pullman and Dr. Marras have no relevant relationships to disclose.
Before getting to work on developing guidelines for genetic testing in Parkinson’s disease, a task force of the Movement Disorders Society surveyed members worldwide to identify concerns they have about using genetic testing in practice. In results presented as a late-breaking abstract at the International Congress of Parkinson’s Disease and Movement Disorders,
“Some of the major outstanding issues are the clinical actionability of genetic testing – and this was highlighted by some survey participants,” senior study author Rachel Saunders-Pullman, MD, MPH, professor of neurology at the Icahn School of Medicine at Mount Sinai, New York, said in an interview. The issue is “dynamic,” and will change even more radically when genetic therapies for Parkinson’s disease become available. “It is planned that, in the development of the MDS Task Force guidelines, scenarios which outline the changes in consideration of testing will depend on the availability of clinically actionable data,” she said.
Barriers to genetic testing
The MDS Task Force for Genetic Testing in Parkinson Disease conducted the survey, completed online by 568 MDS members. Respondents were from the four regions from which the MDS draws members: Africa, Europe, Asia/Oceania, and Pan-America. Half of the respondents considered themselves movement disorder specialists and 31% as general neurologists, said Maggie Markgraf, research coordinator at Mount Sinai Beth Israel in New York, who presented the survey findings.
Barriers to genetic testing that the clinicians cited included cost (57%), lack of availability of genetic counseling (37%), time for testing (20%) or time for counseling (17%). About 14%also cited a lack of knowledge, and only 8.5 % said they saw no barriers for genetic testing. Other concerns included a lack of therapeutic options if tests are positive and low overall positivity rates.
“Perceived barriers for general neurologists differed slightly, with limited knowledge being the most widely reported barrier, followed closely by cost and access to testing and genetic counseling,” Ms. Markgraf said.
Respondents were also asked to identify what they thought their patients perceived as barriers to genetic testing. The major one was cost (65%), followed by limited knowledge about genetics (43%), lack of access to genetic counseling (34%), and lack of access to testing separate from cost (30%). “Across all MDS regions, the perceived level of a patient’s knowledge about genetic testing is considered to be exceedingly low,” Ms. Markgraf said.
Europe had the highest availability to genetic tests, with 41.8% saying they’re accessible to general neurologists, followed by Asia/Oceania (31%) and Pan-America (30%).
“The area of most unmet need when it comes to PD genetic testing was cost for each MDS region, although the intertwined issue of access was also high, and over 50% reported that knowledge was an unmet need in their region,” Dr. Saunders-Pullman said.
Insurance coverage was another issue the survey respondents identified. In Europe, 53.6% said insurance or government programs cover genetic testing for PD, while only 14% in Pan-America and 10.3% in Asia/Oceania (and 0% in Africa) said such coverage was available.
“While there are limitations to this study, greater awareness of availability and barriers to genetic testing and counseling across different regions, as well as disparities among regions, will help inform development of the MDS Task Force guidelines,” Dr. Saunders-Pullman said.
Unmet needs
Connie Marras, MD, PhD, a professor of neurology at the University of Toronto, noted the survey suggested neurologists exhibit a “lack of comfort or lack of time” with genetic testing and counseling for Parkinson’s disease. “Even if we make genetic testing more widely available, we need health care providers that are comfortable and available to counsel patients before and after the testing, and clearly these are unmet needs,” Dr. Marras said in an interview.
“To date, pharmacologic treatment of Parkinson’s disease did not depend on genetics,” Dr. Marras said. “This may well change in the near future with treatments specifically targeting mechanisms related to two of the most common genetic risk factors for PD: LRRK2 and GBA gene variants being in clinical trials.” These developments may soon raise the urgency to reduce barriers to genetic testing.
Dr. Saunders-Pullman and Dr. Marras have no relevant relationships to disclose.
Before getting to work on developing guidelines for genetic testing in Parkinson’s disease, a task force of the Movement Disorders Society surveyed members worldwide to identify concerns they have about using genetic testing in practice. In results presented as a late-breaking abstract at the International Congress of Parkinson’s Disease and Movement Disorders,
“Some of the major outstanding issues are the clinical actionability of genetic testing – and this was highlighted by some survey participants,” senior study author Rachel Saunders-Pullman, MD, MPH, professor of neurology at the Icahn School of Medicine at Mount Sinai, New York, said in an interview. The issue is “dynamic,” and will change even more radically when genetic therapies for Parkinson’s disease become available. “It is planned that, in the development of the MDS Task Force guidelines, scenarios which outline the changes in consideration of testing will depend on the availability of clinically actionable data,” she said.
Barriers to genetic testing
The MDS Task Force for Genetic Testing in Parkinson Disease conducted the survey, completed online by 568 MDS members. Respondents were from the four regions from which the MDS draws members: Africa, Europe, Asia/Oceania, and Pan-America. Half of the respondents considered themselves movement disorder specialists and 31% as general neurologists, said Maggie Markgraf, research coordinator at Mount Sinai Beth Israel in New York, who presented the survey findings.
Barriers to genetic testing that the clinicians cited included cost (57%), lack of availability of genetic counseling (37%), time for testing (20%) or time for counseling (17%). About 14%also cited a lack of knowledge, and only 8.5 % said they saw no barriers for genetic testing. Other concerns included a lack of therapeutic options if tests are positive and low overall positivity rates.
“Perceived barriers for general neurologists differed slightly, with limited knowledge being the most widely reported barrier, followed closely by cost and access to testing and genetic counseling,” Ms. Markgraf said.
Respondents were also asked to identify what they thought their patients perceived as barriers to genetic testing. The major one was cost (65%), followed by limited knowledge about genetics (43%), lack of access to genetic counseling (34%), and lack of access to testing separate from cost (30%). “Across all MDS regions, the perceived level of a patient’s knowledge about genetic testing is considered to be exceedingly low,” Ms. Markgraf said.
Europe had the highest availability to genetic tests, with 41.8% saying they’re accessible to general neurologists, followed by Asia/Oceania (31%) and Pan-America (30%).
“The area of most unmet need when it comes to PD genetic testing was cost for each MDS region, although the intertwined issue of access was also high, and over 50% reported that knowledge was an unmet need in their region,” Dr. Saunders-Pullman said.
Insurance coverage was another issue the survey respondents identified. In Europe, 53.6% said insurance or government programs cover genetic testing for PD, while only 14% in Pan-America and 10.3% in Asia/Oceania (and 0% in Africa) said such coverage was available.
“While there are limitations to this study, greater awareness of availability and barriers to genetic testing and counseling across different regions, as well as disparities among regions, will help inform development of the MDS Task Force guidelines,” Dr. Saunders-Pullman said.
Unmet needs
Connie Marras, MD, PhD, a professor of neurology at the University of Toronto, noted the survey suggested neurologists exhibit a “lack of comfort or lack of time” with genetic testing and counseling for Parkinson’s disease. “Even if we make genetic testing more widely available, we need health care providers that are comfortable and available to counsel patients before and after the testing, and clearly these are unmet needs,” Dr. Marras said in an interview.
“To date, pharmacologic treatment of Parkinson’s disease did not depend on genetics,” Dr. Marras said. “This may well change in the near future with treatments specifically targeting mechanisms related to two of the most common genetic risk factors for PD: LRRK2 and GBA gene variants being in clinical trials.” These developments may soon raise the urgency to reduce barriers to genetic testing.
Dr. Saunders-Pullman and Dr. Marras have no relevant relationships to disclose.
FROM MDS VIRTUAL CONGRESS 2021
Premature menopause a ‘warning sign’ for greater ASCVD risk
Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.
Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.
The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.
The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
‘Surprising’ finding
However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”
She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”
Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.
Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.
“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.
Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.
Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.
Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.
The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.
The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
‘Surprising’ finding
However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”
She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”
Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.
Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.
“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.
Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.
Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.
Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.
The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.
The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
‘Surprising’ finding
However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”
She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”
Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.
Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.
“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.
Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.
FROM JAMA CARDIOLOGY
Walnuts lowered LDL cholesterol in healthy seniors: WAHA study
Benefit sustained over 2 years
Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.
“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.
WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.
The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.
Study results
The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:
- Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
- LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
- Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
- Total LDL cholesterol particles, a reduction of 4.3%.
- Small LDL cholesterol particle number, a 6.1% decrease.
“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.
Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).
Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”
Potential study limitations
Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.
Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”
Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”
Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”
The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.
Benefit sustained over 2 years
Benefit sustained over 2 years
Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.
“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.
WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.
The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.
Study results
The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:
- Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
- LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
- Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
- Total LDL cholesterol particles, a reduction of 4.3%.
- Small LDL cholesterol particle number, a 6.1% decrease.
“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.
Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).
Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”
Potential study limitations
Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.
Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”
Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”
Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”
The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.
Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.
“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.
WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.
The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.
Study results
The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:
- Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
- LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
- Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
- Total LDL cholesterol particles, a reduction of 4.3%.
- Small LDL cholesterol particle number, a 6.1% decrease.
“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.
Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).
Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”
Potential study limitations
Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.
Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”
Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”
Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”
The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.
FROM CIRCULATION