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Alzheimer’s Transmissible Via Stem Cell Transplantation?
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM STEM CELL REPORTS
ASCO Releases Vaccination Guidelines for Adults With Cancer
TOPLINE:
“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines.
METHODOLOGY:
- “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote.
- The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts.
- The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies.
- Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies.
- The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer.
TAKEAWAY:
- The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment.
- The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT.
- After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months.
- After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines.
- Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe.
IN PRACTICE:
“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”
SOURCE:
Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.
LIMITATIONS:
The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.
DISCLOSURES:
This research had no commercial funding. Disclosures for the guideline panel are available with the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines.
METHODOLOGY:
- “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote.
- The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts.
- The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies.
- Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies.
- The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer.
TAKEAWAY:
- The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment.
- The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT.
- After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months.
- After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines.
- Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe.
IN PRACTICE:
“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”
SOURCE:
Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.
LIMITATIONS:
The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.
DISCLOSURES:
This research had no commercial funding. Disclosures for the guideline panel are available with the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines.
METHODOLOGY:
- “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote.
- The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts.
- The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies.
- Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies.
- The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer.
TAKEAWAY:
- The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment.
- The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT.
- After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months.
- After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines.
- Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe.
IN PRACTICE:
“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”
SOURCE:
Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.
LIMITATIONS:
The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.
DISCLOSURES:
This research had no commercial funding. Disclosures for the guideline panel are available with the original article.
A version of this article appeared on Medscape.com.
FDA OKs First-in-Class Agent for Pulmonary Arterial Hypertension
The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.
“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.
The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.
The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).
Sotatercept also led to significant improvement in multiple secondary outcome measures, including:
- Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001)
- Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001)
- Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm5 reduction in PVR from baseline (P < .001)
- Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001)
The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine.
Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.
Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm3.
Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required.
Full prescribing information is available online.
Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.
“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.
The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.
The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).
Sotatercept also led to significant improvement in multiple secondary outcome measures, including:
- Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001)
- Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001)
- Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm5 reduction in PVR from baseline (P < .001)
- Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001)
The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine.
Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.
Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm3.
Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required.
Full prescribing information is available online.
Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved sotatercept (Winrevair, Merck), for the treatment of adults with pulmonary arterial hypertension (PAH), World Health Organization (WHO) Group 1, to increase exercise capacity, improve WHO functional class, and reduce the risk for clinical worsening events.
“Sotatercept added to background therapy has the potential to become a new standard-of-care option for patients with pulmonary arterial hypertension,” added coinvestigator Aaron B. Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital, Boston.
The approval was based on results of the phase 3 STELLAR study, a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which, 323 patients with PAH (WHO Group 1, functional class II or III) were randomly assigned 1:1 to add sotatercept or placebo to stable background therapy.
The results showed that sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved average 6-minute walk distance from baseline by a significant and clinically meaningful 40.8 meters compared with placebo for the trial’s primary efficacy endpoint (P < .001).
Sotatercept also led to significant improvement in multiple secondary outcome measures, including:
- Reduction in the risk for death from any cause or PAH clinical worsening events by 84% vs background therapy alone (number of events: 9 vs 42; hazard ratio [HR], 0.16; P < .001)
- Improvement in FC from baseline at 24 weeks in 29% of patients compared with 14% of patients treated with placebo (P < .001)
- Improvement in pulmonary vascular resistance (PVR), with an average 235 dyn/sec/cm5 reduction in PVR from baseline (P < .001)
- Improvement from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between sotatercept and placebo was -442 pg/mL (P < .001)
The results were reported last year at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, with simultaneous publication in The New England Journal of Medicine.
Sotatercept injection may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider. The recommended starting dose is 0.3 mg/kg. The recommended target dose is 0.7 mg/kg every 3 weeks.
Sotatercept may increase hemoglobin, may lead to erythrocytosis, and may decrease platelet count and lead to severe thrombocytopenia. Treatment should not be initiated if platelet count is < 50,000/mm3.
Hemoglobin and platelets should be monitored before each dose of sotatercept for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required.
Full prescribing information is available online.
Merck estimates that sotatercept will be available for dispensing by select specialty pharmacies in the United States by the end of April 2024.
A version of this article appeared on Medscape.com.
Common Household Chemicals Tied to Brain Cell Damage
Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn.
Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland.
“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.
The results were published online on March 25 in Nature Neuroscience.
Motor Dysfunction
Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells.
The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.
They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.
In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).
After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).
Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2).
“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.
“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said.
In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
Too Soon to Tell
Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research.
“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said.
“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned.
“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said.
Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.
“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.
“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added.
The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures.
A version of this article appeared on Medscape.com.
Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn.
Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland.
“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.
The results were published online on March 25 in Nature Neuroscience.
Motor Dysfunction
Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells.
The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.
They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.
In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).
After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).
Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2).
“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.
“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said.
In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
Too Soon to Tell
Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research.
“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said.
“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned.
“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said.
Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.
“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.
“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added.
The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures.
A version of this article appeared on Medscape.com.
Two classes of chemicals present in common household products may impair the development of oligodendrocytes, the myelinating cells of the central nervous system (CNS), which are critical to brain development and function. However, the researchers as well as outside experts agree more research is needed before any firm conclusions can be drawn.
Quaternary ammonium compounds, ubiquitous in disinfecting agents and personal care products, and organophosphate flame retardants, which are commonly found in household items such as furniture and electronics had “surprising effects specifically on the non-nerve cells in the brain,” said lead researcher Paul Tesar, PhD, professor and director of the Institute for Glial Sciences, Case Western Reserve University School of Medicine, Cleveland.
“Other studies have shown that our exposures to the chemicals in disinfecting agents nearly doubled during the pandemic,” Dr. Tesar noted. The finding that quaternary ammonium chemicals in disinfecting agents are harmful to specific brain cells suggests “we need to think about our increased utilization and exposure,” he added.
The results were published online on March 25 in Nature Neuroscience.
Motor Dysfunction
Exposure to various chemicals in the environment has been shown to impair brain development. However, most of this research has focused on neurons. Less is known about effects on oligodendrocytes, which form the electrical insulation around the axons of CNS cells.
The researchers analyzed the effects of 1823 chemicals on mouse oligodendrocyte development in cell cultures. They identified 292 chemicals that cause oligodendrocytes to die and 47 that inhibit oligodendrocyte generation. These chemicals belonged to two different classes.
They found that quaternary compounds were potently and selectively cytotoxic to developing oligodendrocytes and that organophosphate flame retardants prematurely arrested oligodendrocyte maturation. These effects were confirmed in mice and cultured human oligodendrocytes.
In addition, an analysis of epidemiologic data from the National Health and Nutrition Examination Survey (2013-2018) showed that one flame retardant metabolite, bis(1,3-dichloro-2-propy) phosphate (BDCIPP), was present in nearly all urine samples of children aged 3-11 years who were examined (1753 out of 1763 children).
After adjustment for multiple confounding factors, results showed that compared with children with urinary BDCIPP concentration in the lowest quartile, those with concentrations in the highest quartile were twice as likely to require special education (adjusted odds ratio [aOR], 2.0; 95% CI, 1.0-3.8) and were six times as likely to have gross motor dysfunction (aOR, 6.0; 95% CI, 1.7-21.9).
Children with urinary BDCIPP concentration within the third quartile also had significantly increased odds of motor dysfunction (aOR, 4.2; 95% CI, 1.1-16.2).
“These results suggest that the identified chemicals are potentially hazardous to human health. However, we want to be clear that more studies are needed to make definitive connections between chemical exposure and human disease,” said Dr. Tesar.
“Future studies will need to deepen our understanding of the duration and timing of exposure required to initiate or exacerbate disease. This information is needed before specific recommendations, such as behavioral interventions, can be made to reduce exposure. Some of these chemicals have useful roles in our homes, but we need to consider how they’re being used and what level of exposure might be considered safe,” Dr. Tesar said.
In his view, the results “provide a starting point to understand what exposure levels to these chemicals might be putting ourselves or kids at risk for toxicity.”
Too Soon to Tell
Commenting for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, who was not involved in the study, echoed the need for more research.
“The biological mechanisms uncovered provide plausible pathways by which these chemicals could potentially impact human brain development related to oligodendrocytes and myelination. Oligodendrocytes play a critical role in plastic neurological processes throughout life, not just early neurodevelopment. So, disrupting their maturation and function theoretically could contribute to neurodevelopmental disorders as well as adult conditions like multiple sclerosis,” Dr. Lakhan said.
“This study alone shouldn’t sound neurotoxicant alarms yet. We’ve seen many past chemical scares like saccharin and phthalates fizzle despite alarming lab results when real-world human brain impacts failed to materialize,” Dr. Lakhan cautioned.
“Far more rigorous research directly linking household chemical exposures to cognitive deficits in people is still needed before drawing firm conclusions or prompting overreactions from the general public. Policymakers will eventually need to weigh potential risks vs benefits, but no definitive human health threat has currently been established,” Dr. Lakhan said.
Sarah Evans, PhD, MPH, assistant professor in the Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York, also emphasized the need for further study.
“Given that most of the experiments in this study were conducted in isolated cells and a mouse model, further research is needed to determine whether exposure to these chemicals at levels experienced by the general population during critical windows of development impairs myelination and leads to adverse health outcomes like learning and behavior problems in humans,” said Dr. Evans, who was involved in the study.
“The authors’ finding of an association between higher urinary levels of the organophosphate flame-retardant metabolite BDCIPP and gross motor problems or need for special education in children aged 3-11 years in the CDC National Health and Nutrition Examination Survey strengthens their laboratory findings and warrants further investigation,” Dr. Evans added.
The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society, Howard Hughes Medical Institute and New York Stem Cell Foundation, and philanthropic support by sTF5 Care and the Long, Walter, Peterson, Goodman, and Geller families. Dr. Tesar, Dr. Lakhan, and Dr. Evans report no relevant disclosures.
A version of this article appeared on Medscape.com.
New Data: Black Women More Likely to Die From Common Endometrial Cancer Subtype
A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.
In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.
“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.
Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.
Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.
Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.
Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.
All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.
Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.
When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).
In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).
When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.
Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).
Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.
One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»
The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.
The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.
David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”
“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.
A version of this article appeared on Medscape.com .
A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.
In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.
“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.
Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.
Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.
Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.
Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.
All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.
Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.
When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).
In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).
When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.
Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).
Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.
One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»
The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.
The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.
David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”
“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.
A version of this article appeared on Medscape.com .
A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.
In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.
“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.
Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.
Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.
Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.
Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.
All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.
Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.
When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).
In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).
When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.
Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).
Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.
One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»
The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.
The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.
David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”
“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.
A version of this article appeared on Medscape.com .
FROM SGO 2024
Human Brains Are Getting Bigger: Good News for Dementia Risk?
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
Infant Exposure to MS Drugs via Breastfeeding: New Data
, new research confirmed.
Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.
“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.
“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Registry Data and Analysis
Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).
Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).
Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.
The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.
In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.
A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
‘Reassuring’ Data
Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”
Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”
“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.
“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”
In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.
The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research confirmed.
Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.
“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.
“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Registry Data and Analysis
Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).
Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).
Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.
The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.
In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.
A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
‘Reassuring’ Data
Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”
Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”
“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.
“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”
In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.
The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research confirmed.
Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.
“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.
“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Registry Data and Analysis
Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).
Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).
Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.
The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.
In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.
A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
‘Reassuring’ Data
Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”
Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”
“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.
“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”
In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.
The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.
A version of this article appeared on Medscape.com.
Gaps Found in Appropriate SGLT2, GLP-1 Prescribing
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.
First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.
The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.
“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
Low Prescription Rates
In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.
Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.
The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).
Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.
Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).
“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.
“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.
Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.
The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.
In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.
Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.
“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.
“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
‘Concerning’ Data Raise Key Questions
The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.
“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.
“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.
Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.
Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.
Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.
SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.
“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.
“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.
In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”
“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.
None of the studies had commercial funding. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.
First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.
The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.
“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
Low Prescription Rates
In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.
Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.
The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).
Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.
Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).
“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.
“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.
Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.
The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.
In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.
Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.
“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.
“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
‘Concerning’ Data Raise Key Questions
The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.
“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.
“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.
Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.
Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.
Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.
SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.
“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.
“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.
In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”
“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.
None of the studies had commercial funding. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.
First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.
The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.
“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
Low Prescription Rates
In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.
Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.
The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).
Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.
Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).
“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.
“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.
Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.
The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.
In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.
Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.
“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.
“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
‘Concerning’ Data Raise Key Questions
The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.
“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.
“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.
Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.
Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.
Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.
SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.
“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.
“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.
In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”
“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.
None of the studies had commercial funding. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
Sleep Apnea Is Hard on the Brain
, results from a large study showed.
Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.
“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Need to Raise Awareness
The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.
Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.
Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).
“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.
Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
Consistent Data
Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.
For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.
“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.
Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.
The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
A version of this article appeared on Medscape.com.
, results from a large study showed.
Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.
“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Need to Raise Awareness
The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.
Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.
Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).
“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.
Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
Consistent Data
Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.
For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.
“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.
Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.
The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
A version of this article appeared on Medscape.com.
, results from a large study showed.
Data from a representative sample of US adults show that those who reported sleep apnea symptoms were about 50% more likely to also report cognitive issues versus their counterparts without such symptoms.
“For clinicians, these findings suggest a potential benefit of considering sleep apnea as a possible contributing or exacerbating factor in individuals experiencing memory or cognitive problems. This could prompt further evaluation for sleep apnea, particularly in at-risk individuals,” said study investigator Dominique Low, MD, MPH, Department of Neurology, Boston Medical Center.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Need to Raise Awareness
The findings are based on 4257 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey and completed questionnaires covering sleep, memory, cognition, and decision-making abilities.
Those who reported snorting, gasping, or breathing pauses during sleep were categorized as experiencing sleep apnea symptoms. Those who reported memory trouble, periods of confusion, difficulty concentrating, or decision-making problems were classified as having memory or cognitive symptoms.
Overall, 1079 participants reported symptoms of sleep apnea. Compared with people without sleep apnea, those with symptoms were more likely to have cognitive problems (33% vs 20%) and have greater odds of having memory or cognitive symptoms, even after adjusting for age, gender, race, and education (adjusted odds ratio, 2.02; P < .001).
“While the study did not establish a cause-and-effect relationship, the findings suggest the importance of raising awareness about the potential link between sleep and cognitive function. Early identification and treatment may improve overall health and potentially lead to a better quality of life,” Dr. Low said.
Limitations of the study include self-reported data on sleep apnea symptoms and cognitive issues sourced from one survey.
Consistent Data
Reached for comment, Matthew Pase, PhD, with the Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, said the results are similar to earlier work that found a link between obstructive sleep apnea and cognition.
For example, in a recent study, the presence of mild to severe OSA, identified using overnight polysomnography in five community-based cohorts with more than 5900 adults, was associated with poorer cognitive test performance, Dr. Pase said.
“These and other results underscore the importance of healthy sleep for optimal brain health. Future research is needed to test if treating OSA and other sleep disorders can reduce the risk of cognitive impairment,” Dr. Pase said.
Yet, in its latest statement on the topic, the US Preventive Services Task Force concluded there remains insufficient evidence to weigh the balance of benefits and harms of screening for OSA among asymptomatic adults and those with unrecognized symptoms.
The study had no specific funding. Dr. Low and Dr. Pase had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAN 2024
Billions Spent on DMD Meds Despite Scant Proof of Efficacy
Three genetically targeted drugs for Duchenne muscular dystrophy (DMD) — eteplirsen, golodirsen, and casimersen — cost the US health care system more than $3 billion between 2016 and 2022, despite a lack of confirmatory efficacy data, a new analysis showed.
“We were certainly surprised to see how much was spent on these drugs during the period when we were still waiting for evidence to confirm whether or not they were effective,” study investigator Benjamin Rome, MD, MPH, with the Program on Regulation, Therapeutics, and Law, Harvard Medical School and Brigham and Women’s Hospital, Boston, told this news organization.
“With these drugs often costing over $1 million a year, these results show how spending can add up even for drugs that treat a rare disease,” Dr. Rome added.
The study was published online March 11, 2024, in JAMA.
No Confirmatory Research
Investigators estimated public and private spending on eteplirsen, golodirsen, and casimersen for DMD during 2016 and 2022 — years in which these drugs were marketed without the required confirmatory studies completed.
Annual net sales, which include rebates and statutory discounts to Medicaid or 340B entities, for the three drugs totaled $3.1 billion during the study period. Estimated Medicaid and Medicare spending accounted for $1.2 billion of that total. Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).
Overall sales for the drugs increased from $7 million in 2016 to $879 million in 2022, while Medicaid and Medicare spending rose from $25 million in 2017 to $327 million in 2022.
Most of the spending on these therapies was for eteplirsen ($2.6 billion [82%]), “the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval,” the authors noted.
Of the total amount spent on the three drugs, US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen.
The findings point to the importance of follow up on drugs that are approved with preliminary evidence, Rome said.
“Congress and the US Food and Drug Administration have already made some important changes to the accelerated approval pathway, so hopefully we won’t see cases of multi-year delays in the future,” he said.
“Payers, including public payers like Medicare and Medicaid, need tools to financially encourage companies to complete the follow-up trials, such as paying less for drugs with accelerated approval or engaging in outcomes-based contracts to ensure they don’t pay billions of dollars for drugs that ultimately turn out not to be effective,” Dr. Rome added.
Reached for comment, Adam C. Powell, PhD, president, Payer+Provider Syndicate, noted that when a condition impacts a small population, as is the case with muscular dystrophy, there are fewer people over which to spread the cost of treatment development.
Dr. Powell pointed to a recent report that showed the average cost of developing a new drug exceeds $2 billion. The finding in the current study, that three DMD treatments had combined net sales of $3.1 billion over a 7-year period, “suggests that their developers may not have yet recouped their development costs,” Dr. Powell told this news organization.
“Unless the cost of drug development can be lessened through innovations in artificial intelligence or other means, high spending per patient for drugs addressing uncommon conditions is to be expected,” noted Dr. Powell, who was not part of the study.
“That said, it is concerning when substantial funds are being spent by public payers on treatments that do not work,” he added. “As the authors suggest, one option is to tie reimbursement to efficacy. While patients living with deadly conditions cannot indefinitely wait for treatments to be validated, clawing back payments in the event of inefficacy is always an option.”
The study was funded by Arnold Ventures. Dr. Rome reported receiving grants from the Elevance Health Public Policy Institute, the National Academy for State Health Policy, and several state prescription drug affordability boards outside the submitted work. Powell had no relevant disclosures.
A version of this article appeared on Medscape.com .
Three genetically targeted drugs for Duchenne muscular dystrophy (DMD) — eteplirsen, golodirsen, and casimersen — cost the US health care system more than $3 billion between 2016 and 2022, despite a lack of confirmatory efficacy data, a new analysis showed.
“We were certainly surprised to see how much was spent on these drugs during the period when we were still waiting for evidence to confirm whether or not they were effective,” study investigator Benjamin Rome, MD, MPH, with the Program on Regulation, Therapeutics, and Law, Harvard Medical School and Brigham and Women’s Hospital, Boston, told this news organization.
“With these drugs often costing over $1 million a year, these results show how spending can add up even for drugs that treat a rare disease,” Dr. Rome added.
The study was published online March 11, 2024, in JAMA.
No Confirmatory Research
Investigators estimated public and private spending on eteplirsen, golodirsen, and casimersen for DMD during 2016 and 2022 — years in which these drugs were marketed without the required confirmatory studies completed.
Annual net sales, which include rebates and statutory discounts to Medicaid or 340B entities, for the three drugs totaled $3.1 billion during the study period. Estimated Medicaid and Medicare spending accounted for $1.2 billion of that total. Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).
Overall sales for the drugs increased from $7 million in 2016 to $879 million in 2022, while Medicaid and Medicare spending rose from $25 million in 2017 to $327 million in 2022.
Most of the spending on these therapies was for eteplirsen ($2.6 billion [82%]), “the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval,” the authors noted.
Of the total amount spent on the three drugs, US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen.
The findings point to the importance of follow up on drugs that are approved with preliminary evidence, Rome said.
“Congress and the US Food and Drug Administration have already made some important changes to the accelerated approval pathway, so hopefully we won’t see cases of multi-year delays in the future,” he said.
“Payers, including public payers like Medicare and Medicaid, need tools to financially encourage companies to complete the follow-up trials, such as paying less for drugs with accelerated approval or engaging in outcomes-based contracts to ensure they don’t pay billions of dollars for drugs that ultimately turn out not to be effective,” Dr. Rome added.
Reached for comment, Adam C. Powell, PhD, president, Payer+Provider Syndicate, noted that when a condition impacts a small population, as is the case with muscular dystrophy, there are fewer people over which to spread the cost of treatment development.
Dr. Powell pointed to a recent report that showed the average cost of developing a new drug exceeds $2 billion. The finding in the current study, that three DMD treatments had combined net sales of $3.1 billion over a 7-year period, “suggests that their developers may not have yet recouped their development costs,” Dr. Powell told this news organization.
“Unless the cost of drug development can be lessened through innovations in artificial intelligence or other means, high spending per patient for drugs addressing uncommon conditions is to be expected,” noted Dr. Powell, who was not part of the study.
“That said, it is concerning when substantial funds are being spent by public payers on treatments that do not work,” he added. “As the authors suggest, one option is to tie reimbursement to efficacy. While patients living with deadly conditions cannot indefinitely wait for treatments to be validated, clawing back payments in the event of inefficacy is always an option.”
The study was funded by Arnold Ventures. Dr. Rome reported receiving grants from the Elevance Health Public Policy Institute, the National Academy for State Health Policy, and several state prescription drug affordability boards outside the submitted work. Powell had no relevant disclosures.
A version of this article appeared on Medscape.com .
Three genetically targeted drugs for Duchenne muscular dystrophy (DMD) — eteplirsen, golodirsen, and casimersen — cost the US health care system more than $3 billion between 2016 and 2022, despite a lack of confirmatory efficacy data, a new analysis showed.
“We were certainly surprised to see how much was spent on these drugs during the period when we were still waiting for evidence to confirm whether or not they were effective,” study investigator Benjamin Rome, MD, MPH, with the Program on Regulation, Therapeutics, and Law, Harvard Medical School and Brigham and Women’s Hospital, Boston, told this news organization.
“With these drugs often costing over $1 million a year, these results show how spending can add up even for drugs that treat a rare disease,” Dr. Rome added.
The study was published online March 11, 2024, in JAMA.
No Confirmatory Research
Investigators estimated public and private spending on eteplirsen, golodirsen, and casimersen for DMD during 2016 and 2022 — years in which these drugs were marketed without the required confirmatory studies completed.
Annual net sales, which include rebates and statutory discounts to Medicaid or 340B entities, for the three drugs totaled $3.1 billion during the study period. Estimated Medicaid and Medicare spending accounted for $1.2 billion of that total. Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).
Overall sales for the drugs increased from $7 million in 2016 to $879 million in 2022, while Medicaid and Medicare spending rose from $25 million in 2017 to $327 million in 2022.
Most of the spending on these therapies was for eteplirsen ($2.6 billion [82%]), “the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval,” the authors noted.
Of the total amount spent on the three drugs, US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen.
The findings point to the importance of follow up on drugs that are approved with preliminary evidence, Rome said.
“Congress and the US Food and Drug Administration have already made some important changes to the accelerated approval pathway, so hopefully we won’t see cases of multi-year delays in the future,” he said.
“Payers, including public payers like Medicare and Medicaid, need tools to financially encourage companies to complete the follow-up trials, such as paying less for drugs with accelerated approval or engaging in outcomes-based contracts to ensure they don’t pay billions of dollars for drugs that ultimately turn out not to be effective,” Dr. Rome added.
Reached for comment, Adam C. Powell, PhD, president, Payer+Provider Syndicate, noted that when a condition impacts a small population, as is the case with muscular dystrophy, there are fewer people over which to spread the cost of treatment development.
Dr. Powell pointed to a recent report that showed the average cost of developing a new drug exceeds $2 billion. The finding in the current study, that three DMD treatments had combined net sales of $3.1 billion over a 7-year period, “suggests that their developers may not have yet recouped their development costs,” Dr. Powell told this news organization.
“Unless the cost of drug development can be lessened through innovations in artificial intelligence or other means, high spending per patient for drugs addressing uncommon conditions is to be expected,” noted Dr. Powell, who was not part of the study.
“That said, it is concerning when substantial funds are being spent by public payers on treatments that do not work,” he added. “As the authors suggest, one option is to tie reimbursement to efficacy. While patients living with deadly conditions cannot indefinitely wait for treatments to be validated, clawing back payments in the event of inefficacy is always an option.”
The study was funded by Arnold Ventures. Dr. Rome reported receiving grants from the Elevance Health Public Policy Institute, the National Academy for State Health Policy, and several state prescription drug affordability boards outside the submitted work. Powell had no relevant disclosures.
A version of this article appeared on Medscape.com .