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U.S. incidence, prevalence of myasthenia gravis is rising
, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained.
Claims-based analysis
To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.
They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.
Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.
Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.
For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.
When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.
In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).
Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.
The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.
These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.
A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
Underestimated burden
Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”
“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”
“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.
“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added.
Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.
A version of this article originally appeared on Medscape.com.
, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained.
Claims-based analysis
To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.
They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.
Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.
Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.
For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.
When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.
In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).
Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.
The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.
These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.
A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
Underestimated burden
Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”
“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”
“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.
“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added.
Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.
A version of this article originally appeared on Medscape.com.
, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.
Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.
Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.
In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained.
Claims-based analysis
To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.
They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.
Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.
Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.
For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.
When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.
In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).
Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.
The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.
These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.
A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
Underestimated burden
Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”
“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”
“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.
“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added.
Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.
A version of this article originally appeared on Medscape.com.
From AAN 2023
Head-to-head comparison of migraine meds reveals top options
BOSTON – , a new real-world analysis of data on more than 3 million migraine attacks shows.
The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
The power of big data
Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.
“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.
The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.
They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).
The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.
The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.
Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).
Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).
This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
End of trial-and-error?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”
“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.
“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.
The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , a new real-world analysis of data on more than 3 million migraine attacks shows.
The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
The power of big data
Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.
“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.
The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.
They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).
The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.
The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.
Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).
Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).
This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
End of trial-and-error?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”
“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.
“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.
The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , a new real-world analysis of data on more than 3 million migraine attacks shows.
The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
The power of big data
Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.
“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.
The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.
They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).
The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.
The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.
Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).
Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).
This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
End of trial-and-error?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”
“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.
“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.
The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AAN 2023
Oral antiamyloid shows disease-modifying potential Phase 3 trial underway
BOSTON – , represented by positive changes in plasma and imaging biomarkers of Alzheimer’s disease pathology.
Use of the drug, ALZ-801 (Alzheon), led to a significant reduction of plasma phosphorylated–tau 181 (p-tau181) , a marker of amyloid-induced neuronal injury in Alzheimer’s disease, as well as slowing of hippocampal atrophy and stabilization of cognition.
“The 12-month results of our phase 2 trial support the finding that ALZ-801 blocks misfolding of amyloid monomers and subsequent formation of neurotoxic amyloid oligomers, the key initial step in the amyloid aggregation cascade, which leads to a rapid and sustained reduction of brain neurodegeneration as measured by plasma p-tau181,” John Hey, PhD, Alzheon’s chief scientific officer, said in a statement.
“The severalfold greater reduction on the p-tau181 biomarker in plasma compared to plaque-clearing antiamyloid antibodies, combined with preservation of brain hippocampal volume and their positive correlations with cognitive benefits, further validate the disease-modifying effects of ALZ-801 in Alzheimer’s patients,” Dr. Hey added.
The results were presented at the 2023 annual meeting of the American Academy of Neurology.
ALZ-801 is an optimized prodrug of tramiprosate that has been shown to inhibit amyloid-beta 42 aggregation into toxic oligomers.
The ongoing phase 2 study is evaluating the effects of oral ALZ-801 (265 mg twice daily) on biomarkers of Alzheimer’s disease pathology for 84 adults with early Alzheimer’s disease who have either the APOE4/4 or APOE3/4 genotype. These genotypes represent the majority of patients with Alzheimer’s disease.
The mean age of the cohort was 69 years, and 51% are women; 70% had mild cognitive impairment, and 30% had mild Alzheimer’s disease. The mean Mini-Mental State Examination score for the cohort was 26.0. Roughly half were taking a cholinesterase inhibitor.
Significant plasma p-tau181 reduction was observed at 13 weeks. Levels were reduced by 41% by 52 weeks (P = .016). There was also a significant 5% reduction in plasma amyloid-beta 42 and 40 at 52 weeks (P = .002 and P = .005, respectively), Dr. Hey reported.
After 12 months of treatment, hippocampal atrophy was reduced by about 23%, and expansion of ventricular volume was reduced by about 15%, both in comparison with matched controls from the Alzheimer’s Disease Neuroimaging Initiative.
Composite cognitive z-score improved significantly at 13 and 26 weeks and remained above baseline at 52 weeks in comparison with matched ADNI controls. “These are very promising data,” Dr. Hey told conference attendees.
He noted that the safety profile of ALZ-801 remains favorable and consistent with prior safety data. Common adverse events were mild nausea and SARS-CoV-2 infection. There were no drug-related serious events or amyloid-related imaging abnormalities–edema (ARIA-E).
The phase 3 APOLLOE4 study of ALZ-801 is underway. This double-blind, randomized study is comparing oral ALZ-801 with placebo over 78 weeks for roughly 300 adults with early Alzheimer’s disease who have the APOE4/4 genotype. APOLLOE4 is expected to be completed in mid 2024.
The APOLLOE4 study is supported by a $47 million grant from the National Institute on Aging. The U.S. Food and Drug Administration has granted ALZ-801 fast-track designation.
More accessible option?
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, noted that the “biggest difference between this drug and others is that it is taken orally, rather than delivered through an infusion. This is important and valuable for reducing patient and caregiver burden and increasing ease of use and access.”
It’s also noteworthy that ALZ-801 was not associated with ARIA-E, “which has been reported in other antiamyloid trials and can occasionally be serious,” Dr. Griffin said.
Overall, he said the results are “encouraging, but more work is needed. If studies results continue to be positive, this treatment may provide a more accessible option for people who are at higher risk of ARIA,” Dr. Griffin said.
The study was funded by Alzheon. Dr. Hey is an employee of Alzheon and holds stock in the company. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , represented by positive changes in plasma and imaging biomarkers of Alzheimer’s disease pathology.
Use of the drug, ALZ-801 (Alzheon), led to a significant reduction of plasma phosphorylated–tau 181 (p-tau181) , a marker of amyloid-induced neuronal injury in Alzheimer’s disease, as well as slowing of hippocampal atrophy and stabilization of cognition.
“The 12-month results of our phase 2 trial support the finding that ALZ-801 blocks misfolding of amyloid monomers and subsequent formation of neurotoxic amyloid oligomers, the key initial step in the amyloid aggregation cascade, which leads to a rapid and sustained reduction of brain neurodegeneration as measured by plasma p-tau181,” John Hey, PhD, Alzheon’s chief scientific officer, said in a statement.
“The severalfold greater reduction on the p-tau181 biomarker in plasma compared to plaque-clearing antiamyloid antibodies, combined with preservation of brain hippocampal volume and their positive correlations with cognitive benefits, further validate the disease-modifying effects of ALZ-801 in Alzheimer’s patients,” Dr. Hey added.
The results were presented at the 2023 annual meeting of the American Academy of Neurology.
ALZ-801 is an optimized prodrug of tramiprosate that has been shown to inhibit amyloid-beta 42 aggregation into toxic oligomers.
The ongoing phase 2 study is evaluating the effects of oral ALZ-801 (265 mg twice daily) on biomarkers of Alzheimer’s disease pathology for 84 adults with early Alzheimer’s disease who have either the APOE4/4 or APOE3/4 genotype. These genotypes represent the majority of patients with Alzheimer’s disease.
The mean age of the cohort was 69 years, and 51% are women; 70% had mild cognitive impairment, and 30% had mild Alzheimer’s disease. The mean Mini-Mental State Examination score for the cohort was 26.0. Roughly half were taking a cholinesterase inhibitor.
Significant plasma p-tau181 reduction was observed at 13 weeks. Levels were reduced by 41% by 52 weeks (P = .016). There was also a significant 5% reduction in plasma amyloid-beta 42 and 40 at 52 weeks (P = .002 and P = .005, respectively), Dr. Hey reported.
After 12 months of treatment, hippocampal atrophy was reduced by about 23%, and expansion of ventricular volume was reduced by about 15%, both in comparison with matched controls from the Alzheimer’s Disease Neuroimaging Initiative.
Composite cognitive z-score improved significantly at 13 and 26 weeks and remained above baseline at 52 weeks in comparison with matched ADNI controls. “These are very promising data,” Dr. Hey told conference attendees.
He noted that the safety profile of ALZ-801 remains favorable and consistent with prior safety data. Common adverse events were mild nausea and SARS-CoV-2 infection. There were no drug-related serious events or amyloid-related imaging abnormalities–edema (ARIA-E).
The phase 3 APOLLOE4 study of ALZ-801 is underway. This double-blind, randomized study is comparing oral ALZ-801 with placebo over 78 weeks for roughly 300 adults with early Alzheimer’s disease who have the APOE4/4 genotype. APOLLOE4 is expected to be completed in mid 2024.
The APOLLOE4 study is supported by a $47 million grant from the National Institute on Aging. The U.S. Food and Drug Administration has granted ALZ-801 fast-track designation.
More accessible option?
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, noted that the “biggest difference between this drug and others is that it is taken orally, rather than delivered through an infusion. This is important and valuable for reducing patient and caregiver burden and increasing ease of use and access.”
It’s also noteworthy that ALZ-801 was not associated with ARIA-E, “which has been reported in other antiamyloid trials and can occasionally be serious,” Dr. Griffin said.
Overall, he said the results are “encouraging, but more work is needed. If studies results continue to be positive, this treatment may provide a more accessible option for people who are at higher risk of ARIA,” Dr. Griffin said.
The study was funded by Alzheon. Dr. Hey is an employee of Alzheon and holds stock in the company. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , represented by positive changes in plasma and imaging biomarkers of Alzheimer’s disease pathology.
Use of the drug, ALZ-801 (Alzheon), led to a significant reduction of plasma phosphorylated–tau 181 (p-tau181) , a marker of amyloid-induced neuronal injury in Alzheimer’s disease, as well as slowing of hippocampal atrophy and stabilization of cognition.
“The 12-month results of our phase 2 trial support the finding that ALZ-801 blocks misfolding of amyloid monomers and subsequent formation of neurotoxic amyloid oligomers, the key initial step in the amyloid aggregation cascade, which leads to a rapid and sustained reduction of brain neurodegeneration as measured by plasma p-tau181,” John Hey, PhD, Alzheon’s chief scientific officer, said in a statement.
“The severalfold greater reduction on the p-tau181 biomarker in plasma compared to plaque-clearing antiamyloid antibodies, combined with preservation of brain hippocampal volume and their positive correlations with cognitive benefits, further validate the disease-modifying effects of ALZ-801 in Alzheimer’s patients,” Dr. Hey added.
The results were presented at the 2023 annual meeting of the American Academy of Neurology.
ALZ-801 is an optimized prodrug of tramiprosate that has been shown to inhibit amyloid-beta 42 aggregation into toxic oligomers.
The ongoing phase 2 study is evaluating the effects of oral ALZ-801 (265 mg twice daily) on biomarkers of Alzheimer’s disease pathology for 84 adults with early Alzheimer’s disease who have either the APOE4/4 or APOE3/4 genotype. These genotypes represent the majority of patients with Alzheimer’s disease.
The mean age of the cohort was 69 years, and 51% are women; 70% had mild cognitive impairment, and 30% had mild Alzheimer’s disease. The mean Mini-Mental State Examination score for the cohort was 26.0. Roughly half were taking a cholinesterase inhibitor.
Significant plasma p-tau181 reduction was observed at 13 weeks. Levels were reduced by 41% by 52 weeks (P = .016). There was also a significant 5% reduction in plasma amyloid-beta 42 and 40 at 52 weeks (P = .002 and P = .005, respectively), Dr. Hey reported.
After 12 months of treatment, hippocampal atrophy was reduced by about 23%, and expansion of ventricular volume was reduced by about 15%, both in comparison with matched controls from the Alzheimer’s Disease Neuroimaging Initiative.
Composite cognitive z-score improved significantly at 13 and 26 weeks and remained above baseline at 52 weeks in comparison with matched ADNI controls. “These are very promising data,” Dr. Hey told conference attendees.
He noted that the safety profile of ALZ-801 remains favorable and consistent with prior safety data. Common adverse events were mild nausea and SARS-CoV-2 infection. There were no drug-related serious events or amyloid-related imaging abnormalities–edema (ARIA-E).
The phase 3 APOLLOE4 study of ALZ-801 is underway. This double-blind, randomized study is comparing oral ALZ-801 with placebo over 78 weeks for roughly 300 adults with early Alzheimer’s disease who have the APOE4/4 genotype. APOLLOE4 is expected to be completed in mid 2024.
The APOLLOE4 study is supported by a $47 million grant from the National Institute on Aging. The U.S. Food and Drug Administration has granted ALZ-801 fast-track designation.
More accessible option?
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, noted that the “biggest difference between this drug and others is that it is taken orally, rather than delivered through an infusion. This is important and valuable for reducing patient and caregiver burden and increasing ease of use and access.”
It’s also noteworthy that ALZ-801 was not associated with ARIA-E, “which has been reported in other antiamyloid trials and can occasionally be serious,” Dr. Griffin said.
Overall, he said the results are “encouraging, but more work is needed. If studies results continue to be positive, this treatment may provide a more accessible option for people who are at higher risk of ARIA,” Dr. Griffin said.
The study was funded by Alzheon. Dr. Hey is an employee of Alzheon and holds stock in the company. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAN 2023
CPAP not only solution for sleep apnea
Although continuous positive airway pressure (CPAP) machines are the gold standard in the management of sleep apnea, several other treatments should be considered.
“Just because you have a hammer doesn’t mean everything is a nail,” Kimberly Hardin, MD, professor of clinical internal medicine at University of California, Davis, said at the annual meeting of the American College of Physicians.
“Sleep has been underestimated in the health arena for many, many years,” said Dr. Hardin, who likened sound sleep to the “sixth vital sign.” “We know that sleep plays an integral role in our health.”
Surgical options include nasal surgery and maxillomandibular advancement surgery, also known as double-jaw surgery. Such procedures should be considered only for patients who are unwilling or unable to use CPAP or other nonsurgical treatments.
Sleep apnea occurs in 4% of adult men and 2% of adult women aged 30-60. Most commonly, obstructive sleep apnea involves the cessation or significant decrease in airflow while sleeping. The Apnea Hypopnea Index (AHI) is the number of times a patient experiences apnea or hypopnea during one night divided by the hours of sleep. Normal sleep AHI is fewer than five events per hour on average; mild sleep apnea is five to 14 events; moderate, 15-29; and severe, at least 30 events.
To identify sleep apnea, physicians have several tools at their disposal, starting with preliminary questionnaires that query patients as to whether they are having trouble falling asleep, staying asleep, or are tired during the day. Additional assessment tools include sleep lab testing and at-home testing.
At-home testing has come to include more than the common devices that are worn around the chest and nose for a night.
“It’s not very fun looking,” Dr. Hardin said of the weighty, obtrusive monitoring devices. “So lots of folks have come up with some new ways of doing things.”
These new options incorporate headbands, wrist and finger devices, arterial tonometry, and sleep rings.
Studies show that U.S. adults do not get enough sleep, and poor-quality sleep is as inadequate as insufficient sleep. Barely a third of adults get the minimum 7 hours recommended by the Centers for Disease Control and Prevention. Non-Hispanic Black adults are less likely to report sleeping 7-9 hours and are more likely to report sleeping 6 or fewer hours than are non-Hispanic White and Hispanic adults.
Dr. Hardin said doctors can advise patients to keep their bedrooms quiet, dark, and cool with no TVs or electronics, to maintain regular wake and sleep times, and to stop consuming caffeine late in the day.
Insufficient or poor sleep can have wide-ranging implications on medical conditions such as diabetes, heart disease, obesity, immunodeficiency, cognitive function, mental health, and, ultimately, mortality, according to Dr. Hardin.
“Some people say, ‘Oh, never mind, I can sleep when I’m dead,’ “ Dr. Hardin said. But such a mentality can have a bearing on life expectancy.
A version of this article first appeared on Medscape.com.
Although continuous positive airway pressure (CPAP) machines are the gold standard in the management of sleep apnea, several other treatments should be considered.
“Just because you have a hammer doesn’t mean everything is a nail,” Kimberly Hardin, MD, professor of clinical internal medicine at University of California, Davis, said at the annual meeting of the American College of Physicians.
“Sleep has been underestimated in the health arena for many, many years,” said Dr. Hardin, who likened sound sleep to the “sixth vital sign.” “We know that sleep plays an integral role in our health.”
Surgical options include nasal surgery and maxillomandibular advancement surgery, also known as double-jaw surgery. Such procedures should be considered only for patients who are unwilling or unable to use CPAP or other nonsurgical treatments.
Sleep apnea occurs in 4% of adult men and 2% of adult women aged 30-60. Most commonly, obstructive sleep apnea involves the cessation or significant decrease in airflow while sleeping. The Apnea Hypopnea Index (AHI) is the number of times a patient experiences apnea or hypopnea during one night divided by the hours of sleep. Normal sleep AHI is fewer than five events per hour on average; mild sleep apnea is five to 14 events; moderate, 15-29; and severe, at least 30 events.
To identify sleep apnea, physicians have several tools at their disposal, starting with preliminary questionnaires that query patients as to whether they are having trouble falling asleep, staying asleep, or are tired during the day. Additional assessment tools include sleep lab testing and at-home testing.
At-home testing has come to include more than the common devices that are worn around the chest and nose for a night.
“It’s not very fun looking,” Dr. Hardin said of the weighty, obtrusive monitoring devices. “So lots of folks have come up with some new ways of doing things.”
These new options incorporate headbands, wrist and finger devices, arterial tonometry, and sleep rings.
Studies show that U.S. adults do not get enough sleep, and poor-quality sleep is as inadequate as insufficient sleep. Barely a third of adults get the minimum 7 hours recommended by the Centers for Disease Control and Prevention. Non-Hispanic Black adults are less likely to report sleeping 7-9 hours and are more likely to report sleeping 6 or fewer hours than are non-Hispanic White and Hispanic adults.
Dr. Hardin said doctors can advise patients to keep their bedrooms quiet, dark, and cool with no TVs or electronics, to maintain regular wake and sleep times, and to stop consuming caffeine late in the day.
Insufficient or poor sleep can have wide-ranging implications on medical conditions such as diabetes, heart disease, obesity, immunodeficiency, cognitive function, mental health, and, ultimately, mortality, according to Dr. Hardin.
“Some people say, ‘Oh, never mind, I can sleep when I’m dead,’ “ Dr. Hardin said. But such a mentality can have a bearing on life expectancy.
A version of this article first appeared on Medscape.com.
Although continuous positive airway pressure (CPAP) machines are the gold standard in the management of sleep apnea, several other treatments should be considered.
“Just because you have a hammer doesn’t mean everything is a nail,” Kimberly Hardin, MD, professor of clinical internal medicine at University of California, Davis, said at the annual meeting of the American College of Physicians.
“Sleep has been underestimated in the health arena for many, many years,” said Dr. Hardin, who likened sound sleep to the “sixth vital sign.” “We know that sleep plays an integral role in our health.”
Surgical options include nasal surgery and maxillomandibular advancement surgery, also known as double-jaw surgery. Such procedures should be considered only for patients who are unwilling or unable to use CPAP or other nonsurgical treatments.
Sleep apnea occurs in 4% of adult men and 2% of adult women aged 30-60. Most commonly, obstructive sleep apnea involves the cessation or significant decrease in airflow while sleeping. The Apnea Hypopnea Index (AHI) is the number of times a patient experiences apnea or hypopnea during one night divided by the hours of sleep. Normal sleep AHI is fewer than five events per hour on average; mild sleep apnea is five to 14 events; moderate, 15-29; and severe, at least 30 events.
To identify sleep apnea, physicians have several tools at their disposal, starting with preliminary questionnaires that query patients as to whether they are having trouble falling asleep, staying asleep, or are tired during the day. Additional assessment tools include sleep lab testing and at-home testing.
At-home testing has come to include more than the common devices that are worn around the chest and nose for a night.
“It’s not very fun looking,” Dr. Hardin said of the weighty, obtrusive monitoring devices. “So lots of folks have come up with some new ways of doing things.”
These new options incorporate headbands, wrist and finger devices, arterial tonometry, and sleep rings.
Studies show that U.S. adults do not get enough sleep, and poor-quality sleep is as inadequate as insufficient sleep. Barely a third of adults get the minimum 7 hours recommended by the Centers for Disease Control and Prevention. Non-Hispanic Black adults are less likely to report sleeping 7-9 hours and are more likely to report sleeping 6 or fewer hours than are non-Hispanic White and Hispanic adults.
Dr. Hardin said doctors can advise patients to keep their bedrooms quiet, dark, and cool with no TVs or electronics, to maintain regular wake and sleep times, and to stop consuming caffeine late in the day.
Insufficient or poor sleep can have wide-ranging implications on medical conditions such as diabetes, heart disease, obesity, immunodeficiency, cognitive function, mental health, and, ultimately, mortality, according to Dr. Hardin.
“Some people say, ‘Oh, never mind, I can sleep when I’m dead,’ “ Dr. Hardin said. But such a mentality can have a bearing on life expectancy.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2023
FDA expands atogepant approval to include chronic migraine
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
Malaria: Not just someone else’s problem
What is the most dangerous animal on Earth? Which one has killed more humans since we first began walking upright?
The mind leaps to the vicious and dangerous – great white sharks. lions. tigers. crocodiles. The fearsome predators of the planet But realistically, more people are killed and injured by large herbivores each year than predators. Just watch news updates from Yellowstone during their busy season.
Anyway, the correct answer is ... none of the above.
It’s the mosquito, and the many microbes it’s a vector for. Malaria, in particular. Even the once-devastating bubonic plague is no longer a major concern.
What do Presidents Washington, Kennedy, Eisenhower, Lincoln, Monroe, Grant, Garfield, Jackson, Teddy Roosevelt, and other historical VIPs like Oliver Cromwell, King Tut, and numerous kings, queens, and popes all have in common? They all had malaria. Cromwell, Tut, and many royal and religious figures died of it.
You can make a solid argument that malaria is the disease that’s affected the course of history more than any other (you could make a good case for the plague, too, but it’s less relevant today). The control of malaria is what allowed the Panama canal to happen.
I’m bringing this up because, mostly overlooked in the news recently as we argued about light beer endorsements, TV pundits, and the NFL draft, is the approval and gradual increase in use of a malaria vaccine.
This is a pretty big deal given the scope of the problem and the fact that the most effective prevention up until recently was a mosquito net.
We tend to see malaria as someone else’s problem, something that affects the tropics, but forget that as recently as the 1940s it was still common in the U.S. During the Civil War as many as 1 million soldiers were infected with it. Given the right conditions it could easily return here.
Which is why we should be more aware of these things. As COVID showed, infectious diseases are never some other country’s, or continent’s, problem. They affect all of us either directly or indirectly. In the interconnected economies of the world illnesses in one area can spread to others. Even if they don’t they can still have significant effects on supply chains, since so much of what we depend on comes from somewhere else.
COVID, by comparison, is small beer. Just think about smallpox, or the plague, or polio, as to what an unchecked disease can do to a society until medicine catches up with it.
There will always be new diseases. Microbes and humans have been in a state of hostilities for a few million years now, and likely always will be. But every victory along the way is a victory for everyone, regardless of who they are or where they live.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
What is the most dangerous animal on Earth? Which one has killed more humans since we first began walking upright?
The mind leaps to the vicious and dangerous – great white sharks. lions. tigers. crocodiles. The fearsome predators of the planet But realistically, more people are killed and injured by large herbivores each year than predators. Just watch news updates from Yellowstone during their busy season.
Anyway, the correct answer is ... none of the above.
It’s the mosquito, and the many microbes it’s a vector for. Malaria, in particular. Even the once-devastating bubonic plague is no longer a major concern.
What do Presidents Washington, Kennedy, Eisenhower, Lincoln, Monroe, Grant, Garfield, Jackson, Teddy Roosevelt, and other historical VIPs like Oliver Cromwell, King Tut, and numerous kings, queens, and popes all have in common? They all had malaria. Cromwell, Tut, and many royal and religious figures died of it.
You can make a solid argument that malaria is the disease that’s affected the course of history more than any other (you could make a good case for the plague, too, but it’s less relevant today). The control of malaria is what allowed the Panama canal to happen.
I’m bringing this up because, mostly overlooked in the news recently as we argued about light beer endorsements, TV pundits, and the NFL draft, is the approval and gradual increase in use of a malaria vaccine.
This is a pretty big deal given the scope of the problem and the fact that the most effective prevention up until recently was a mosquito net.
We tend to see malaria as someone else’s problem, something that affects the tropics, but forget that as recently as the 1940s it was still common in the U.S. During the Civil War as many as 1 million soldiers were infected with it. Given the right conditions it could easily return here.
Which is why we should be more aware of these things. As COVID showed, infectious diseases are never some other country’s, or continent’s, problem. They affect all of us either directly or indirectly. In the interconnected economies of the world illnesses in one area can spread to others. Even if they don’t they can still have significant effects on supply chains, since so much of what we depend on comes from somewhere else.
COVID, by comparison, is small beer. Just think about smallpox, or the plague, or polio, as to what an unchecked disease can do to a society until medicine catches up with it.
There will always be new diseases. Microbes and humans have been in a state of hostilities for a few million years now, and likely always will be. But every victory along the way is a victory for everyone, regardless of who they are or where they live.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
What is the most dangerous animal on Earth? Which one has killed more humans since we first began walking upright?
The mind leaps to the vicious and dangerous – great white sharks. lions. tigers. crocodiles. The fearsome predators of the planet But realistically, more people are killed and injured by large herbivores each year than predators. Just watch news updates from Yellowstone during their busy season.
Anyway, the correct answer is ... none of the above.
It’s the mosquito, and the many microbes it’s a vector for. Malaria, in particular. Even the once-devastating bubonic plague is no longer a major concern.
What do Presidents Washington, Kennedy, Eisenhower, Lincoln, Monroe, Grant, Garfield, Jackson, Teddy Roosevelt, and other historical VIPs like Oliver Cromwell, King Tut, and numerous kings, queens, and popes all have in common? They all had malaria. Cromwell, Tut, and many royal and religious figures died of it.
You can make a solid argument that malaria is the disease that’s affected the course of history more than any other (you could make a good case for the plague, too, but it’s less relevant today). The control of malaria is what allowed the Panama canal to happen.
I’m bringing this up because, mostly overlooked in the news recently as we argued about light beer endorsements, TV pundits, and the NFL draft, is the approval and gradual increase in use of a malaria vaccine.
This is a pretty big deal given the scope of the problem and the fact that the most effective prevention up until recently was a mosquito net.
We tend to see malaria as someone else’s problem, something that affects the tropics, but forget that as recently as the 1940s it was still common in the U.S. During the Civil War as many as 1 million soldiers were infected with it. Given the right conditions it could easily return here.
Which is why we should be more aware of these things. As COVID showed, infectious diseases are never some other country’s, or continent’s, problem. They affect all of us either directly or indirectly. In the interconnected economies of the world illnesses in one area can spread to others. Even if they don’t they can still have significant effects on supply chains, since so much of what we depend on comes from somewhere else.
COVID, by comparison, is small beer. Just think about smallpox, or the plague, or polio, as to what an unchecked disease can do to a society until medicine catches up with it.
There will always be new diseases. Microbes and humans have been in a state of hostilities for a few million years now, and likely always will be. But every victory along the way is a victory for everyone, regardless of who they are or where they live.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Researchers seek to understand post-COVID autoimmune disease risk
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Since the COVID-19 pandemic started more than 3 years ago, the longer-lasting effects of SARS-CoV-2 infection have continued to reveal themselves. Approximately 28% of Americans report having ever experienced post-COVID conditions, such as brain fog, postexertional malaise, and joint pain, and 11% say they are still experiencing these long-term effects. Now, new research is showing that people who have had COVID are more likely to newly develop an autoimmune disease. Exactly why this is happening is less clear, experts say.
Two preprint studies and one study published in a peer-reviewed journal provide strong evidence that patients who have been infected with SARS-CoV-2 are at elevated risk of developing an autoimmune disease. The studies retrospectively reviewed medical records from three countries and compared the incidence of new-onset autoimmune disease among patients who had polymerase chain reaction–confirmed COVID-19 and those who had never been diagnosed with the virus.
A study analyzing the health records of 3.8 million U.S. patients – more than 888,460 with confirmed COVID-19 – found that the COVID-19 group was two to three times as likely to develop various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. A U.K. preprint study that included more than 458,000 people with confirmed COVID found that those who had previously been infected with SARS-CoV-2 were 22% more likely to develop an autoimmune disease compared with the control group. In this cohort, the diseases most strongly associated with COVID-19 were type 1 diabetes, inflammatory bowel disease, and psoriasis. A preprint study from German researchers found that COVID-19 patients were almost 43% more likely to develop an autoimmune disease, compared with those who had never been infected. COVID-19 was most strongly linked to vasculitis.
These large studies are telling us, “Yes, this link is there, so we have to accept it,” Sonia Sharma, PhD, of the Center for Autoimmunity and Inflammation at the La Jolla (Calif.) Institute for Immunology, told this news organization. But this is not the first time that autoimmune diseases have been linked to previous infections.
Researchers have known for decades that Epstein-Barr virus infection is linked to several autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. More recent research suggests the virus may activate certain genes associated with these immune disorders. Hepatitis C virus can induce cryoglobulinemia, and infection with cytomegalovirus has been implicated in several autoimmune diseases. Bacterial infections have also been linked to autoimmunity, such as group A streptococcus and rheumatic fever, as well as salmonella and reactive arthritis, to name only a few.
“In a way, this isn’t necessarily a new concept to physicians, particularly rheumatologists,” said Jeffrey A. Sparks, MD, a rheumatologist at Brigham and Women’s Hospital in Boston. “There’s a fine line between appropriately clearing an infection and the body overreacting and setting off a cascade where the immune system is chronically overactive that can manifest as an autoimmune disease,” he told this news organization.
A dysregulated response to infection
It takes the immune system a week or two to develop antigen-specific antibodies to a new pathogen. But for patients with serious infections – in this instance, COVID-19 – that’s time they don’t have. Therefore, the immune system has an alternative pathway, called extrafollicular activation, that creates fast-acting antibodies, explained Matthew Woodruff, PhD, an instructor of immunology and rheumatology at Emory University, Atlanta.
The trade-off is that these antibodies are not as specific and can target the body’s own tissues. This dysregulation of antibody selection is generally short lived and fades when more targeted antibodies are produced and take over, but in some cases, this process can lead to high levels of self-targeting antibodies that can harm the body’s organs and tissues. Research also suggests that for patients who experience long COVID, the same autoantibodies that drive the initial immune response are detectable in the body months after infection, though it is not known whether these lingering immune cells cause these longer-lasting symptoms.
“If you have a virus that causes hyperinflammation plus organ damage, that is a recipe for disaster,” Dr. Sharma said. “It’s a recipe for autoantibodies and autoreactive T cells that down the road can attack the body’s own tissues, especially in people whose immune system is trained in such a way to cause self-reactivity,” she added.
This hyperinflammation can result in rare but serious complications, such as multisystem inflammatory syndrome in children and adults, which can occur 2-6 weeks after SARS-CoV-2 infection. But even in these patients with severe illness, organ-specific complications tend to resolve in 6 months with “no significant sequelae 1 year after diagnosis,” according to the Centers for Disease Control and Prevention. And while long COVID can last for a year or longer, data suggest that symptoms do eventually resolve for most people. What is not clear is why acute autoimmunity triggered by COVID-19 can become a chronic condition in certain patients.
Predisposition to autoimmunity
P. J. Utz, MD, PhD, professor of immunology and rheumatology at Stanford (Calif.) University, said that people who develop autoimmune disease after SARS-CoV-2 infection may have already been predisposed toward autoimmunity. Especially for autoimmune diseases such as type 1 diabetes and lupus, autoantibodies can appear and circulate in the body for more than a decade in some people before they present with any clinical symptoms. “Their immune system is primed such that if they get infected with something – or they have some other environmental trigger that maybe we don’t know about yet – that is enough to then push them over the edge so that they get full-blown autoimmunity,” he said. What is not known is whether these patients’ conditions would have advanced to true clinical disease had they not been infected, he said.
He also noted that the presence of autoantibodies does not necessarily mean someone has autoimmune disease; healthy people can also have autoantibodies, and everyone develops them with age. “My advice would be, ‘Don’t lose sleep over this,’ “ he said.
Dr. Sparks agreed that while these retrospective studies did show an elevated risk of autoimmune disease after COVID-19, that risk appears to be relatively small. “As a practicing rheumatologist, we aren’t seeing a stampede of patients with new-onset rheumatic diseases,” he said. “It’s not like we’re overwhelmed with autoimmune patients, even though almost everyone’s had COVID. So, if there is a risk, it’s very modest.”
Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care. Dr. Utz receives research funding from Pfizer. Dr. Sharma and Dr. Woodruff have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Donanemab bests aducanumab in head-to-head Alzheimer’s trial
BOSTON –
Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.
Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.
Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.
“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
Multicenter, head-to-head trial
Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.
TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.
Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.
Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.
After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).
Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).
Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).
Investigators also noted a greater reduction in plasma ptau217 with donanemab.
Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.
There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.
“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.
There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.
That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.
The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.
“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.
Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
Questions remain
“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.
Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”
Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.
“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.
It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.
“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”
The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON –
Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.
Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.
Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.
“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
Multicenter, head-to-head trial
Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.
TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.
Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.
Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.
After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).
Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).
Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).
Investigators also noted a greater reduction in plasma ptau217 with donanemab.
Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.
There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.
“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.
There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.
That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.
The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.
“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.
Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
Questions remain
“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.
Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”
Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.
“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.
It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.
“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”
The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON –
Nearly 40% of patients treated with donanemab had amyloid clearance at 6 months compared with less than 2% of those who received aducanumab, which was approved in 2021 amid a great deal of controversy.
Titration for donanemab progressed more quickly, with participants receiving a maximum dose twice as early as those on aducanumab, without any increase in rates of amyloid-related imaging abnormalities (ARIA) – the most common side effect of amyloid drugs.
Early results from the randomized phase 3 TRAILBLAZER-ALZ 4 trial of donanemab come just 3 months after the Food and Drug Administration denied manufacturer Eli Lilly’s request for accelerated approval for the drug.
“This study shows that the drug with the quicker titration scheme, donanemab, produced more amyloid lowering and did it without having more ARIA,” said lead investigator Stephen P. Salloway, MD, director of the Memory and Aging Program at Butler Hospital in Providence, R.I., and a professor of neurology at Brown University.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
Multicenter, head-to-head trial
Donanemab received breakthrough therapy designation in 2021. The drug works similarly to aducanumab and lecanemab, which was approved earlier this year. All three bind to different parts of the amyloid molecule and stimulate an immune response to help clear amyloid plaques, although they each have a distinctive binding component.
TRAILBLAZER-ALZ 4 was conducted at 31 sites across the United States, enrolling 140 patients aged 50-85 years with early and symptomatic Alzheimer’s disease. Study participants received donanemab or aducanumab at escalating doses for 18 months.
Donanemab was titrated more quickly, with participants receiving 700 mg via IV infusion once a month for 3 months before reaching the maximum dose of 1,400 mg in the fourth month of the study.
Aducanumab titration was slower, beginning at 1 mg/kg via IV monthly for 2 months, then 3 mg/kg for another 2 months, and 6 mg/kg for 2 more months before reaching the maximum dose of 10 mg/kg in the seventh month.
After 6 months of treatment, PET scan analysis revealed that 37.9% of donanemab-treated patients achieved amyloid clearance compared with just 1.6% of those who received aducanumab (P < .001).
Among patients with intermediate tau levels (n = 27 for donanemab and n = 28 for aducanumab), 38.5% of those who received donanemab achieved amyloid clearance compared with 3.8% of patients in the aducanumab group (P = .008).
Amyloid levels were 65.2% lower in donanemab patients, while levels in those receiving aducanumab were reduced by 17.0% (P < .001). Among those with intermediate tau, amyloid levels decreased with donanemab by 63.9% and 25.4% with aducanumab (P ≤ .001).
Investigators also noted a greater reduction in plasma ptau217 with donanemab.
Adverse events were similar between groups, with 62.0% of the donanemab group and 66.7% of aducanumab-treated participants reporting an adverse event.
There were no serious adverse events due to ARIA with donanemab, but one participant in the aducanumab group had a serious adverse event linked to ARIA.
“Even though the amyloid lowering was greater with donanemab, the rate of ARIA was similar, which suggests that the speed and depth of amyloid removal is not driving ARIA,” Dr. Salloway said.
There are three other Trailblazer trials of donanemab. Unlike in similar trials, participants in all three of these studies who received the trial drug could discontinue treatment once criteria for amyloid clearance were met.
That’s precisely what happened with Trailblazer 2, the study on which Lilly based its request for accelerated approval. Ironically, that trial design also contributed to the FDA’s decision to reject that request.
The FDA required data from at least 100 patients who had received donanemab for a minimum of 1 year. While the trial included more than 100 patients, many patients discontinued treatment early after achieving the targeted amount of amyloid clearance.
“They had success, and they got punished for it, in my opinion,” Dr. Salloway said.
Final data from Trailblazer 2 is due in the next month, and if results are positive, Lilly is expected to file for full approval.
Questions remain
“This is an interesting study that suggests donanemab may remove amyloid faster in more people than aducanumab,” said Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings.
Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, also commented on the findings. He noted that faster amyloid clearance “means less time for requiring sometimes burdensome and expensive infusions.”
Both Dr. Snyder and Dr. Fillit noted that longer-term results are needed, along with studies of whether amyloid clearance offers a protective benefit against Alzheimer’s dementia. More results from Trailblazer 4 will be reported after 12 months and again at 18 months.
“There are obviously still a lot of questions about these drugs and whether reducing amyloid plaque will actually preserve cognitive function or at least slow decline,” Dr. Fillit said.
It will also be important to understand the timing of treatment, including when anti-amyloid therapies should be administered and for how long.
“It will be important to understand how these results translate to patient care and treatment plans, should this drug receive FDA approval,” Dr. Snyder said. “Patients should have the opportunity to make a decision, alongside their physician, on a treatment path that is right for them.”
The study was funded by Eli Lilly. Dr. Salloway has been a consultant for Biogen, EISAI, Lilly, Genentech, Novo Nordisk, Prothena, and others. Dr. Snyder and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAN 2023
New hope for adult children with ‘failure to launch’ syndrome
WASHINGTON – , a new pilot study shows.
Known as failure to launch (FTL) syndrome, the criteria for this condition include the absence of a neurodevelopmental, mental, or intellectual condition, difficulty adapting to the challenges of adulthood, and living with or at the expense of parents.
Results suggest that the program benefits families dealing with FTL, said study investigator Uri Berger, PhD, postdoctoral associate, Yale Child Study Center Anxiety and Mood Disorders Program, New Haven, Conn.
“If you encounter parents who are say 50-60 years old who have a child with FTL, you can tell them there’s something they can do; there’s work they can do even if their child is refusing to go to therapy,” he said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Anxious, isolated
Estimates suggest that there are 3.3 million physically able adults with FTL and that the disorder may be on the rise. These individuals often present with mental health symptoms including anxiety, depression, and suicidality, and tend to be socially isolated.
The investigators noted that intervening is often challenging because individuals with the syndrome are frequently noncompliant with therapy, and currently there is no standard of care.
“The longer you’re isolated, the harder it is getting out of your cocoon, and when these adult children get to the point where they seek help, they’re less likely to comply,” he said. However, he noted, this is not because they are lazy; it’s that they’re “very, very anxious.”
Parents and other family members are also negatively affected. Dr. Berger noted that 15% of parents of a child with FTL equate their caregiver burden with having a family member with a chronic physical illness. “It’s huge; parents go through hell and it’s very hard on them. Many believe it is their fault and they feel a lot of shame.”
Supportive Parenting for Anxious Childhood Emotions (SPACE) is a manualized, parent-based program for childhood anxiety and obsessive-compulsive disorder. It has been tested in clinical trials and found to be noninferior to cognitive behavioral therapy for childhood anxiety.
The research adapted it to treat FTL. SPACE-FTL focuses on reducing parents’ family accommodation (FA), a descriptor for a child’s excessive dependence on their parents to help them avoid anxiety-provoking situations.
The study examined the feasibility, acceptability, and treatment satisfaction and its effect on adult child psychopathology symptoms, parents’ FA, and the paternal burden of caring for adult children.
The study included parents (mean age, 59.46 years; 85% female) of 40 adult children with FTL (mean age, 23.51 years; 20% female) from across the United States.
Parents were randomized to a 13-week wait-list or the SPACE-FTL program, which involves 13-20 therapy sessions, depending on the need. The average number of sessions in the study was 15. The program has five key components:
- Providing information emphasizing FTL as not a character flaw but a problem with anxiety.
- Helping parents identify how they accommodate their child’s behavior, and facilitating an environment that encourages independence.
- Getting parents to show acceptance and confidence in their child who’s trying to overcome anxiety when, for example, they seek employment, instead of being overprotective and demanding.
- Focusing on change nonconfrontationally.
- Involving other family, community members, and professionals who can support the parent, child, or both.
The recruitment, treatment sessions, and assessments were all done online. Most participants rated the intervention as highly satisfactory on the Client Satisfaction Questionnaire (CSQ-8; mean score, 27.7 out of a maximum of 32). About 60% of the offspring no longer met full criteria for FTL (P < .001; Cohen’s D = 1.76).
All children of the wait-listed parents still met criteria for FTL.
FTL symptoms decreased significantly in the offspring of the intervention group, as seen in both in the Adult Entitled Dependence Scale (AED; P < .05; Cohen’s D = 0.84); and the Adaptive Behaviors Scale (ABS; P < .05; Cohen’s D = 0.70).
There was no change in anxiety as assessed by the Adult Behavior Checklist (ABCL). But Dr. Berger noted that child anxiety is difficult to assess through parental report.
“This population is self-isolating and parents sometimes don’t know what’s going on,” and ABCL measures may not be “as sensitive as we would have liked them to be,” Dr. Berger said.
Parental burden was significantly decreased as measured by the Zarit Burden Interview (ZBI; P < .05; Cohen’s D = 0.70). In addition, family accommodation decreased significantly as determined by the Family Accommodation Scale–Anxiety (FASA; P < .05; Cohen’s D = 0.70).
Innovative work
In a comment, Jonathan E. Alpert, MD, PhD, chair, department of psychiatry and behavioral sciences, and professor of psychiatry, neuroscience, and pediatrics, Albert Einstein College of Medicine, New York, described the program as “innovative.”
He noted that the SPACE-FTL approach provides parents with education and skills to reduce behaviors that reinforce their child’s avoidance of independent activities. Such behaviors “may inadvertently contribute to the adult child remaining stuck,” he said.
“Through its involvement of parents and use of a structured approach, SPACE-FTL is a very interesting step toward more evidence-based therapies.”
However, he noted that the number of study participants is still “very low” and further work is needed to better characterize this condition and develop effective therapies.
He noted that parents of adult children with FTL should not be judged or blamed. “They have been living with a worrisome problem for years and are simply doing their best to cope as any of us would do.”
In addition, he noted that some adult children aren’t capable of launching because of a serious mental illness or substance use disorder that needs treatment.
It’s unclear just how many adult children have FTL, as the condition lacks formal, agreed-upon clinical and research criteria and a reliable evidence base for treatment, Dr. Alpert said.
“Whatever the actual numbers of FTL, my anecdotal clinical experience suggests that it is a very common problem which is understudied.”
He added that the definitions of FTL should include cultural context. In some groups, it’s quite normal for adults in their 20s, 30s, or even older to live with their parents, Dr. Alpert said.
Dr. Berger and Dr. Albert report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , a new pilot study shows.
Known as failure to launch (FTL) syndrome, the criteria for this condition include the absence of a neurodevelopmental, mental, or intellectual condition, difficulty adapting to the challenges of adulthood, and living with or at the expense of parents.
Results suggest that the program benefits families dealing with FTL, said study investigator Uri Berger, PhD, postdoctoral associate, Yale Child Study Center Anxiety and Mood Disorders Program, New Haven, Conn.
“If you encounter parents who are say 50-60 years old who have a child with FTL, you can tell them there’s something they can do; there’s work they can do even if their child is refusing to go to therapy,” he said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Anxious, isolated
Estimates suggest that there are 3.3 million physically able adults with FTL and that the disorder may be on the rise. These individuals often present with mental health symptoms including anxiety, depression, and suicidality, and tend to be socially isolated.
The investigators noted that intervening is often challenging because individuals with the syndrome are frequently noncompliant with therapy, and currently there is no standard of care.
“The longer you’re isolated, the harder it is getting out of your cocoon, and when these adult children get to the point where they seek help, they’re less likely to comply,” he said. However, he noted, this is not because they are lazy; it’s that they’re “very, very anxious.”
Parents and other family members are also negatively affected. Dr. Berger noted that 15% of parents of a child with FTL equate their caregiver burden with having a family member with a chronic physical illness. “It’s huge; parents go through hell and it’s very hard on them. Many believe it is their fault and they feel a lot of shame.”
Supportive Parenting for Anxious Childhood Emotions (SPACE) is a manualized, parent-based program for childhood anxiety and obsessive-compulsive disorder. It has been tested in clinical trials and found to be noninferior to cognitive behavioral therapy for childhood anxiety.
The research adapted it to treat FTL. SPACE-FTL focuses on reducing parents’ family accommodation (FA), a descriptor for a child’s excessive dependence on their parents to help them avoid anxiety-provoking situations.
The study examined the feasibility, acceptability, and treatment satisfaction and its effect on adult child psychopathology symptoms, parents’ FA, and the paternal burden of caring for adult children.
The study included parents (mean age, 59.46 years; 85% female) of 40 adult children with FTL (mean age, 23.51 years; 20% female) from across the United States.
Parents were randomized to a 13-week wait-list or the SPACE-FTL program, which involves 13-20 therapy sessions, depending on the need. The average number of sessions in the study was 15. The program has five key components:
- Providing information emphasizing FTL as not a character flaw but a problem with anxiety.
- Helping parents identify how they accommodate their child’s behavior, and facilitating an environment that encourages independence.
- Getting parents to show acceptance and confidence in their child who’s trying to overcome anxiety when, for example, they seek employment, instead of being overprotective and demanding.
- Focusing on change nonconfrontationally.
- Involving other family, community members, and professionals who can support the parent, child, or both.
The recruitment, treatment sessions, and assessments were all done online. Most participants rated the intervention as highly satisfactory on the Client Satisfaction Questionnaire (CSQ-8; mean score, 27.7 out of a maximum of 32). About 60% of the offspring no longer met full criteria for FTL (P < .001; Cohen’s D = 1.76).
All children of the wait-listed parents still met criteria for FTL.
FTL symptoms decreased significantly in the offspring of the intervention group, as seen in both in the Adult Entitled Dependence Scale (AED; P < .05; Cohen’s D = 0.84); and the Adaptive Behaviors Scale (ABS; P < .05; Cohen’s D = 0.70).
There was no change in anxiety as assessed by the Adult Behavior Checklist (ABCL). But Dr. Berger noted that child anxiety is difficult to assess through parental report.
“This population is self-isolating and parents sometimes don’t know what’s going on,” and ABCL measures may not be “as sensitive as we would have liked them to be,” Dr. Berger said.
Parental burden was significantly decreased as measured by the Zarit Burden Interview (ZBI; P < .05; Cohen’s D = 0.70). In addition, family accommodation decreased significantly as determined by the Family Accommodation Scale–Anxiety (FASA; P < .05; Cohen’s D = 0.70).
Innovative work
In a comment, Jonathan E. Alpert, MD, PhD, chair, department of psychiatry and behavioral sciences, and professor of psychiatry, neuroscience, and pediatrics, Albert Einstein College of Medicine, New York, described the program as “innovative.”
He noted that the SPACE-FTL approach provides parents with education and skills to reduce behaviors that reinforce their child’s avoidance of independent activities. Such behaviors “may inadvertently contribute to the adult child remaining stuck,” he said.
“Through its involvement of parents and use of a structured approach, SPACE-FTL is a very interesting step toward more evidence-based therapies.”
However, he noted that the number of study participants is still “very low” and further work is needed to better characterize this condition and develop effective therapies.
He noted that parents of adult children with FTL should not be judged or blamed. “They have been living with a worrisome problem for years and are simply doing their best to cope as any of us would do.”
In addition, he noted that some adult children aren’t capable of launching because of a serious mental illness or substance use disorder that needs treatment.
It’s unclear just how many adult children have FTL, as the condition lacks formal, agreed-upon clinical and research criteria and a reliable evidence base for treatment, Dr. Alpert said.
“Whatever the actual numbers of FTL, my anecdotal clinical experience suggests that it is a very common problem which is understudied.”
He added that the definitions of FTL should include cultural context. In some groups, it’s quite normal for adults in their 20s, 30s, or even older to live with their parents, Dr. Alpert said.
Dr. Berger and Dr. Albert report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , a new pilot study shows.
Known as failure to launch (FTL) syndrome, the criteria for this condition include the absence of a neurodevelopmental, mental, or intellectual condition, difficulty adapting to the challenges of adulthood, and living with or at the expense of parents.
Results suggest that the program benefits families dealing with FTL, said study investigator Uri Berger, PhD, postdoctoral associate, Yale Child Study Center Anxiety and Mood Disorders Program, New Haven, Conn.
“If you encounter parents who are say 50-60 years old who have a child with FTL, you can tell them there’s something they can do; there’s work they can do even if their child is refusing to go to therapy,” he said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Anxious, isolated
Estimates suggest that there are 3.3 million physically able adults with FTL and that the disorder may be on the rise. These individuals often present with mental health symptoms including anxiety, depression, and suicidality, and tend to be socially isolated.
The investigators noted that intervening is often challenging because individuals with the syndrome are frequently noncompliant with therapy, and currently there is no standard of care.
“The longer you’re isolated, the harder it is getting out of your cocoon, and when these adult children get to the point where they seek help, they’re less likely to comply,” he said. However, he noted, this is not because they are lazy; it’s that they’re “very, very anxious.”
Parents and other family members are also negatively affected. Dr. Berger noted that 15% of parents of a child with FTL equate their caregiver burden with having a family member with a chronic physical illness. “It’s huge; parents go through hell and it’s very hard on them. Many believe it is their fault and they feel a lot of shame.”
Supportive Parenting for Anxious Childhood Emotions (SPACE) is a manualized, parent-based program for childhood anxiety and obsessive-compulsive disorder. It has been tested in clinical trials and found to be noninferior to cognitive behavioral therapy for childhood anxiety.
The research adapted it to treat FTL. SPACE-FTL focuses on reducing parents’ family accommodation (FA), a descriptor for a child’s excessive dependence on their parents to help them avoid anxiety-provoking situations.
The study examined the feasibility, acceptability, and treatment satisfaction and its effect on adult child psychopathology symptoms, parents’ FA, and the paternal burden of caring for adult children.
The study included parents (mean age, 59.46 years; 85% female) of 40 adult children with FTL (mean age, 23.51 years; 20% female) from across the United States.
Parents were randomized to a 13-week wait-list or the SPACE-FTL program, which involves 13-20 therapy sessions, depending on the need. The average number of sessions in the study was 15. The program has five key components:
- Providing information emphasizing FTL as not a character flaw but a problem with anxiety.
- Helping parents identify how they accommodate their child’s behavior, and facilitating an environment that encourages independence.
- Getting parents to show acceptance and confidence in their child who’s trying to overcome anxiety when, for example, they seek employment, instead of being overprotective and demanding.
- Focusing on change nonconfrontationally.
- Involving other family, community members, and professionals who can support the parent, child, or both.
The recruitment, treatment sessions, and assessments were all done online. Most participants rated the intervention as highly satisfactory on the Client Satisfaction Questionnaire (CSQ-8; mean score, 27.7 out of a maximum of 32). About 60% of the offspring no longer met full criteria for FTL (P < .001; Cohen’s D = 1.76).
All children of the wait-listed parents still met criteria for FTL.
FTL symptoms decreased significantly in the offspring of the intervention group, as seen in both in the Adult Entitled Dependence Scale (AED; P < .05; Cohen’s D = 0.84); and the Adaptive Behaviors Scale (ABS; P < .05; Cohen’s D = 0.70).
There was no change in anxiety as assessed by the Adult Behavior Checklist (ABCL). But Dr. Berger noted that child anxiety is difficult to assess through parental report.
“This population is self-isolating and parents sometimes don’t know what’s going on,” and ABCL measures may not be “as sensitive as we would have liked them to be,” Dr. Berger said.
Parental burden was significantly decreased as measured by the Zarit Burden Interview (ZBI; P < .05; Cohen’s D = 0.70). In addition, family accommodation decreased significantly as determined by the Family Accommodation Scale–Anxiety (FASA; P < .05; Cohen’s D = 0.70).
Innovative work
In a comment, Jonathan E. Alpert, MD, PhD, chair, department of psychiatry and behavioral sciences, and professor of psychiatry, neuroscience, and pediatrics, Albert Einstein College of Medicine, New York, described the program as “innovative.”
He noted that the SPACE-FTL approach provides parents with education and skills to reduce behaviors that reinforce their child’s avoidance of independent activities. Such behaviors “may inadvertently contribute to the adult child remaining stuck,” he said.
“Through its involvement of parents and use of a structured approach, SPACE-FTL is a very interesting step toward more evidence-based therapies.”
However, he noted that the number of study participants is still “very low” and further work is needed to better characterize this condition and develop effective therapies.
He noted that parents of adult children with FTL should not be judged or blamed. “They have been living with a worrisome problem for years and are simply doing their best to cope as any of us would do.”
In addition, he noted that some adult children aren’t capable of launching because of a serious mental illness or substance use disorder that needs treatment.
It’s unclear just how many adult children have FTL, as the condition lacks formal, agreed-upon clinical and research criteria and a reliable evidence base for treatment, Dr. Alpert said.
“Whatever the actual numbers of FTL, my anecdotal clinical experience suggests that it is a very common problem which is understudied.”
He added that the definitions of FTL should include cultural context. In some groups, it’s quite normal for adults in their 20s, 30s, or even older to live with their parents, Dr. Alpert said.
Dr. Berger and Dr. Albert report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2023
Cautious optimism for new Alzheimer’s disease biomarkers and treatments, expert says
SAN DIEGO – said a presenter at the annual meeting of the American College of Physicians.
Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.
Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
Diagnosis of Alzheimer’s disease
The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.
Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.
“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.
It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
Why do we need biomarkers for Alzheimer’s disease?
AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.
“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.
This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta1–42, phosphorylated tau, and neurofilament light chain.
With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”
New and emerging therapies for Alzheimer’s disease
There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.
“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.
Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.
In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”
Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.
Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
Looking ahead
When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.
“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.
Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.
SAN DIEGO – said a presenter at the annual meeting of the American College of Physicians.
Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.
Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
Diagnosis of Alzheimer’s disease
The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.
Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.
“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.
It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
Why do we need biomarkers for Alzheimer’s disease?
AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.
“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.
This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta1–42, phosphorylated tau, and neurofilament light chain.
With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”
New and emerging therapies for Alzheimer’s disease
There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.
“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.
Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.
In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”
Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.
Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
Looking ahead
When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.
“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.
Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.
SAN DIEGO – said a presenter at the annual meeting of the American College of Physicians.
Dementia prevalence is increasing as the proportion of the U.S. population older than 65 rises, said Zaldy Tan, MD, professor of neurology at Cedars-Sinai Medical Center, Los Angeles. AD deaths more than doubled between 2000 and 2018, he noted, while deaths from HIV infection, stroke, and heart disease decreased.
Most people in the United States who have AD are White, but studies suggest that, compared with Whites, the risk of AD is two times higher in Blacks and 1.5 times higher in Hispanics . “These data suggest that both genes and social determinants of health are at play,” Dr. Tan said.
Diagnosis of Alzheimer’s disease
The different types of dementia make it challenging for primary care physicians to identify the cause of cognitive impairment. “Even though AD is the most common type, clinicians should keep in mind that another type of dementia may be the cause of cognitive impairment,” Dr. Tan cautioned. Other dementia diagnoses include vascular, Lewy body, and frontotemporal.
Diagnostic criteria for AD include evidence of significant cognitive decline in at least one cognitive domain that interferes with independence in everyday activities, as well as the absence of another mental disorder or delirium that would explain the cognitive deficits.
“We see many patients with depressive symptoms and mild cognitive impairment, and it is not always easy to tell which of them have dementia because of the overlap in the symptoms of depression and AD,” said internist Roderick Kim, MD, of Grand Rapids, Mich., who attended the session.
It can be challenging to convince patients to undergo the appropriate diagnostic workup, Dr. Kim said. “This can delay treatment, so it is important to explain to patients that cognitive decline can progress quickly and that there are treatment options to slow it down.”
Why do we need biomarkers for Alzheimer’s disease?
AD is characterized by a long preclinical phase with no specific symptoms other than the typical signs and symptoms of aging, Dr. Tan said. That means cognitive impairment progresses rapidly after diagnosis in most patients with AD.
“In most cases, an accurate history, physical and neurologic examinations, basic labs, and neuroimaging are sufficient for memory loss evaluation. However, as more disease-modifying therapies come to market, biomarkers will rise in importance in primary care,” he said.
This long asymptomatic phase of AD creates the need for diagnostic biomarkers for an earlier diagnosis, he said. Amyloid-beta and tau deposits in PET images and the levels of amyloid-beta seeds, phosphorylated tau, and neurofilament light chain in the cerebrospinal fluid can be used as diagnostic biomarkers in patients with suspected AD. Emerging blood biomarkers for earlier detection include the levels of amyloid-beta1–42, phosphorylated tau, and neurofilament light chain.
With biomarkers and other new tools for the diagnosis of dementia in primary care, Dr. Tan said: “The greatest challenge is cost, as blood-based biomarkers are not currently covered by insurance and still rather costly. In addition, blood-based biomarkers will need to receive [Food and Drug Administration] approval in order to have more widespread availability.”
New and emerging therapies for Alzheimer’s disease
There are two classes of FDA-approved medications to manage cognitive symptoms of dementia: acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The selections may be trial and error for each patient, Dr. Tan said.
“The approved medications can exert subtle benefits that are clinically observable. Thus, barring any contraindications or intolerance, most patients with AD would benefit from a trial of one or both of these medication classes,” said Dr. Tan. He added that it is equally important to wean off and discontinue these medications if there is intolerance or lack of a subjective or objective beneficial response.
Other medications are available for some of the most common behavioral problems associated with dementia, such as agitation, depression, and disorientation. Dr. Tan advised not to prescribe behavioral medications until nonpharmacologic interventions prove to be ineffective or impractical. Behavioral medications have many side effects, some of which are potentially serious, he said, so the risk-benefit ratio should be considered.
In his own practice, when nonpharmacologic strategies do not improve the behavioral symptoms of dementia, Dr. Tan said that, “in cases where a person is at risk of harm to themselves or others, a discussion with the patient and their caregivers about the pros and cons of medications to treat the behavior need to be had. Careful monitoring of the response and dose escalation or deprescribing when appropriate is important to keep in mind.”
Disease-modifying agents have recently provided new hope for AD treatment. Aducanumab and lecanemab, both monoclonal antibodies that target amyloids, are the first two drugs that received accelerated FDA approval for AD.
Although these monoclonal antibodies can help clear deposited amyloid plaques and show some benefit in slowing cognitive impairment in clinical trials, the real-world benefits were unclear enough for Medicare to limit coverage to people enrolled in approved studies to gather more data. Additionally, these agents can cause potentially amyloid-related imaging abnormalities, which may indicate edema, effusion, or microhemorrhage. Therefore, clinicians need to have a clear conversation of risks and benefits with patients and caregivers about these treatments.
Looking ahead
When asked about the most promising emerging technologies or techniques related to dementia diagnosis and management, Dr. Tan noted that multiple technology companies and start-ups are looking for new ways to detect dementia earlier or keep persons with dementia safe at home. Some devices deliver brain waves, computerized brain games or tests, automated pill dispensers, and fall monitors.
“Some of these are potentially helpful, but not every person with dementia will benefit. In addition, most of these technologies are out-of-pocket expenses for the patients and their families. It is important to know what is out there but also be cautious about outrageous claims,” he added.
Dr. Tan reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients.
AT INTERNAL MEDICINE 2023