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Smoking Linked to More Genetic Havoc in MDS
The prospective National MDS Natural History Study evaluated 1898 patients with recently diagnosed or suspected MDS. An adjusted analysis linked higher number of pack-years to more mutations (P = .006), with those at the 90th percentile with 3.5 times the number of mutations as nonsmokers, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
The findings “suggest that smoking potentially contributes to the multistep molecular genetic pathogenesis that ultimately results in diagnosis of the cancer,” said corresponding author Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, at a news briefing. “The more you smoke, the more likely you are to acquire more mutations and even develop a higher risk of myelodysplastic syndromes. [More smoking] was also associated with progression and survival.”
While numbers are uncertain, an estimated 10,000 or more people in the United States each year are diagnosed with MDS, also known as preleukemia, according to the American Cancer Society. Median survival ranges from 1 to 10.6 years based on risk group, although the cancer society says the statistics are dated and mainly from Europe.
Multiple studies have linked smoking to MDS. The new study aims to understand the possible effects of smoking on genetic mutations.
The research analyzed 1898 patients enrolled from 2016 to 2023 (52% who had ever smoked; 18% current smokers; mean smoking years, 29.8 ± 16.9 years). The patients had diagnoses of MDSs, MDS/myeloproliferative neoplasm overlap, or precursor conditions such as clonal cytopenia of undetermined significance (CCUS).
Smokers were more likely than nonsmokers to be men (68% vs 54%; P < .001) and aged 70-79 years (45% vs 34%; P < .001).
After adjustment for confounders, smokers had more average mutations linked to MDS than nonsmokers (2.0 vs 1.4; P = .04). Those at the 75th percentile of pack-years had 1.8 times as many MDS-linked mutations as nonsmokers.
The 5-year cumulative incidence of disease progression was higher in long-term smokers than in nonsmokers and those with shorter smoking history (mean proportion progressed, 20+ years vs < 20 years smoking/nonsmoking, 27% [19%-36%] vs 18% [13%-24%]; P < .05, respectively).
Also, overall survival was lower in smokers than in nonsmokers for patients with CCUS (hazard ratio [HR], 1.91; 95% CI, 1.03-3.55; P = .04) but not for those with MDS (HR, 1.21; 95% CI, 0.53-1.30; P = .41).
“The data suggests that a patient with a new diagnosis of MDS who also smokes should be counseled to stop smoking,” Sekeres said.
This may seem counterintuitive to patients, he acknowledged. When Sekeres was a medical student, he counseled a female patient with advanced lung cancer to quit smoking. “The patient looked at me like I had three heads and she said: ‘Why should I stop smoking? The cats are already out of the bag. I have lung cancer.’ ”
But the new study points to a possible benefit from quitting smoking while sick. “It appears that smoking contributes to the acquisition of new genetic mutations that can lead to worsening of the myelodysplastic syndromes and even evolution of the cancer into acute myeloid leukemia,” Sekeres said.
He added: “One thing to understand about these cancers of the bone marrow is they can take years or decades to develop. They’re not one-hit wonders. Smoking caused very specific genetic mutations. The cool part of this is that they’re the same genetic mutations smoking has been shown to cause in cancers like lung cancer, so we’re seeing consistency across cancers.”
Sekeres said he himself will counsel patients with MDS or acute myeloid leukemia to stop smoking. “If there’s anything we can do to intervene to prevent myelodysplastic syndrome from evolving into acute leukemia, my word, I sure I’m going to try it.”
In an interview, Peter Greenberg, MD, professor of medicine at Stanford Cancer Center in California, who’s familiar with the study but didn’t take part in the research, said the study suggests that smoking in MDS isn’t just related to exposure to fumes “but appears to be a much more widespread problem” related to its impact on generating hematologic stem cell mutations.
Most clinicians don’t warn patients with MDS about the dangers of smoking because they’re not aware of tobacco’s connection to the disease, Greenberg said. But there’s another reason to bring up smoking, he said: It boosts the risk for cardiovascular disease, which may be partially responsible for decreased survival in smokers.
Sekeres disclosed ties with Kurome, Schrödinger, and Bristol-Myers Squibb. Other authors reported multiple and various relationships with industry. Greenberg had no disclosures.
A version of this article appeared on Medscape.com.
The prospective National MDS Natural History Study evaluated 1898 patients with recently diagnosed or suspected MDS. An adjusted analysis linked higher number of pack-years to more mutations (P = .006), with those at the 90th percentile with 3.5 times the number of mutations as nonsmokers, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
The findings “suggest that smoking potentially contributes to the multistep molecular genetic pathogenesis that ultimately results in diagnosis of the cancer,” said corresponding author Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, at a news briefing. “The more you smoke, the more likely you are to acquire more mutations and even develop a higher risk of myelodysplastic syndromes. [More smoking] was also associated with progression and survival.”
While numbers are uncertain, an estimated 10,000 or more people in the United States each year are diagnosed with MDS, also known as preleukemia, according to the American Cancer Society. Median survival ranges from 1 to 10.6 years based on risk group, although the cancer society says the statistics are dated and mainly from Europe.
Multiple studies have linked smoking to MDS. The new study aims to understand the possible effects of smoking on genetic mutations.
The research analyzed 1898 patients enrolled from 2016 to 2023 (52% who had ever smoked; 18% current smokers; mean smoking years, 29.8 ± 16.9 years). The patients had diagnoses of MDSs, MDS/myeloproliferative neoplasm overlap, or precursor conditions such as clonal cytopenia of undetermined significance (CCUS).
Smokers were more likely than nonsmokers to be men (68% vs 54%; P < .001) and aged 70-79 years (45% vs 34%; P < .001).
After adjustment for confounders, smokers had more average mutations linked to MDS than nonsmokers (2.0 vs 1.4; P = .04). Those at the 75th percentile of pack-years had 1.8 times as many MDS-linked mutations as nonsmokers.
The 5-year cumulative incidence of disease progression was higher in long-term smokers than in nonsmokers and those with shorter smoking history (mean proportion progressed, 20+ years vs < 20 years smoking/nonsmoking, 27% [19%-36%] vs 18% [13%-24%]; P < .05, respectively).
Also, overall survival was lower in smokers than in nonsmokers for patients with CCUS (hazard ratio [HR], 1.91; 95% CI, 1.03-3.55; P = .04) but not for those with MDS (HR, 1.21; 95% CI, 0.53-1.30; P = .41).
“The data suggests that a patient with a new diagnosis of MDS who also smokes should be counseled to stop smoking,” Sekeres said.
This may seem counterintuitive to patients, he acknowledged. When Sekeres was a medical student, he counseled a female patient with advanced lung cancer to quit smoking. “The patient looked at me like I had three heads and she said: ‘Why should I stop smoking? The cats are already out of the bag. I have lung cancer.’ ”
But the new study points to a possible benefit from quitting smoking while sick. “It appears that smoking contributes to the acquisition of new genetic mutations that can lead to worsening of the myelodysplastic syndromes and even evolution of the cancer into acute myeloid leukemia,” Sekeres said.
He added: “One thing to understand about these cancers of the bone marrow is they can take years or decades to develop. They’re not one-hit wonders. Smoking caused very specific genetic mutations. The cool part of this is that they’re the same genetic mutations smoking has been shown to cause in cancers like lung cancer, so we’re seeing consistency across cancers.”
Sekeres said he himself will counsel patients with MDS or acute myeloid leukemia to stop smoking. “If there’s anything we can do to intervene to prevent myelodysplastic syndrome from evolving into acute leukemia, my word, I sure I’m going to try it.”
In an interview, Peter Greenberg, MD, professor of medicine at Stanford Cancer Center in California, who’s familiar with the study but didn’t take part in the research, said the study suggests that smoking in MDS isn’t just related to exposure to fumes “but appears to be a much more widespread problem” related to its impact on generating hematologic stem cell mutations.
Most clinicians don’t warn patients with MDS about the dangers of smoking because they’re not aware of tobacco’s connection to the disease, Greenberg said. But there’s another reason to bring up smoking, he said: It boosts the risk for cardiovascular disease, which may be partially responsible for decreased survival in smokers.
Sekeres disclosed ties with Kurome, Schrödinger, and Bristol-Myers Squibb. Other authors reported multiple and various relationships with industry. Greenberg had no disclosures.
A version of this article appeared on Medscape.com.
The prospective National MDS Natural History Study evaluated 1898 patients with recently diagnosed or suspected MDS. An adjusted analysis linked higher number of pack-years to more mutations (P = .006), with those at the 90th percentile with 3.5 times the number of mutations as nonsmokers, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
The findings “suggest that smoking potentially contributes to the multistep molecular genetic pathogenesis that ultimately results in diagnosis of the cancer,” said corresponding author Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, at a news briefing. “The more you smoke, the more likely you are to acquire more mutations and even develop a higher risk of myelodysplastic syndromes. [More smoking] was also associated with progression and survival.”
While numbers are uncertain, an estimated 10,000 or more people in the United States each year are diagnosed with MDS, also known as preleukemia, according to the American Cancer Society. Median survival ranges from 1 to 10.6 years based on risk group, although the cancer society says the statistics are dated and mainly from Europe.
Multiple studies have linked smoking to MDS. The new study aims to understand the possible effects of smoking on genetic mutations.
The research analyzed 1898 patients enrolled from 2016 to 2023 (52% who had ever smoked; 18% current smokers; mean smoking years, 29.8 ± 16.9 years). The patients had diagnoses of MDSs, MDS/myeloproliferative neoplasm overlap, or precursor conditions such as clonal cytopenia of undetermined significance (CCUS).
Smokers were more likely than nonsmokers to be men (68% vs 54%; P < .001) and aged 70-79 years (45% vs 34%; P < .001).
After adjustment for confounders, smokers had more average mutations linked to MDS than nonsmokers (2.0 vs 1.4; P = .04). Those at the 75th percentile of pack-years had 1.8 times as many MDS-linked mutations as nonsmokers.
The 5-year cumulative incidence of disease progression was higher in long-term smokers than in nonsmokers and those with shorter smoking history (mean proportion progressed, 20+ years vs < 20 years smoking/nonsmoking, 27% [19%-36%] vs 18% [13%-24%]; P < .05, respectively).
Also, overall survival was lower in smokers than in nonsmokers for patients with CCUS (hazard ratio [HR], 1.91; 95% CI, 1.03-3.55; P = .04) but not for those with MDS (HR, 1.21; 95% CI, 0.53-1.30; P = .41).
“The data suggests that a patient with a new diagnosis of MDS who also smokes should be counseled to stop smoking,” Sekeres said.
This may seem counterintuitive to patients, he acknowledged. When Sekeres was a medical student, he counseled a female patient with advanced lung cancer to quit smoking. “The patient looked at me like I had three heads and she said: ‘Why should I stop smoking? The cats are already out of the bag. I have lung cancer.’ ”
But the new study points to a possible benefit from quitting smoking while sick. “It appears that smoking contributes to the acquisition of new genetic mutations that can lead to worsening of the myelodysplastic syndromes and even evolution of the cancer into acute myeloid leukemia,” Sekeres said.
He added: “One thing to understand about these cancers of the bone marrow is they can take years or decades to develop. They’re not one-hit wonders. Smoking caused very specific genetic mutations. The cool part of this is that they’re the same genetic mutations smoking has been shown to cause in cancers like lung cancer, so we’re seeing consistency across cancers.”
Sekeres said he himself will counsel patients with MDS or acute myeloid leukemia to stop smoking. “If there’s anything we can do to intervene to prevent myelodysplastic syndrome from evolving into acute leukemia, my word, I sure I’m going to try it.”
In an interview, Peter Greenberg, MD, professor of medicine at Stanford Cancer Center in California, who’s familiar with the study but didn’t take part in the research, said the study suggests that smoking in MDS isn’t just related to exposure to fumes “but appears to be a much more widespread problem” related to its impact on generating hematologic stem cell mutations.
Most clinicians don’t warn patients with MDS about the dangers of smoking because they’re not aware of tobacco’s connection to the disease, Greenberg said. But there’s another reason to bring up smoking, he said: It boosts the risk for cardiovascular disease, which may be partially responsible for decreased survival in smokers.
Sekeres disclosed ties with Kurome, Schrödinger, and Bristol-Myers Squibb. Other authors reported multiple and various relationships with industry. Greenberg had no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Fertility Preservation in SCD: Women Have More Complications
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Does Acalabrutinib Fit Into Frontline MCL Therapy?
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
POLARIX: Extended Results Confirm Standard of Care for DLBCL
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP, compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major said in an interview.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann–La Roche/Genentech. Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), and BMS/Celgene (consultancy), among others. Major reported conflicts of interest with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
A version of this article appeared on Medscape.com.
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP, compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major said in an interview.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann–La Roche/Genentech. Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), and BMS/Celgene (consultancy), among others. Major reported conflicts of interest with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
A version of this article appeared on Medscape.com.
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP, compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major said in an interview.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann–La Roche/Genentech. Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), and BMS/Celgene (consultancy), among others. Major reported conflicts of interest with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
A version of this article appeared on Medscape.com.
FROM ASH 2024
Smart Mattress to Reduce SUDEP?
LOS ANGELES — says one of the experts involved in its development.
When used along with a seizure detection device, Jong Woo Lee, MD, PhD, associate professor of neurology, Harvard Medical School, and Brigham and Women’s Hospital, both in Boston, Massachusetts, estimates the smart mattress could cut SUDEP by more than 50%.
In addition, early results from an observational study are backing this up, he said.
The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
Most SUDEP Cases Found Face Down
SUDEP is the leading cause of death in children with epilepsy and in otherwise healthy adult patients with epilepsy. When his fifth patient died of SUDEP, Lee decided it was time to try to tackle the high mortality rate associated with these unexpected deaths. “I desperately wanted to help, ” he said.
About 70% of SUDEP occurs during sleep, and victims are found face down, or in the prone position, 90% of the time, said Lee.
“Of course, the best way to prevent SUDEP is not to have a seizure, but once you have a seizure and once you’re face down, your risk for death goes up by somewhere between 30 and 100 times,” he explained.
Lee was convinced SUDEP could be prevented by simple interventions that stimulate the patient and turn them over. He noted the incidence of sudden infant death syndrome, “which has similar characteristics” to SUDEP, has been reduced by up to 75% through campaigns that simply advise placing babies on their backs.
“Most of SUDEP happens because your arousal system is knocked out and you just don’t take the breath that you’re supposed to. Just the act of turning people over and vibrating the bed will stimulate them,” he said.
However, it’s crucial that this be done quickly, said Lee. “When you look at patients who died on video and see the EEGs, everybody took their last breath within 3 minutes.”
Because the window of opportunity is so short, “we think that seizure detection devices alone are not going to really be effective because you just can’t get there or react within those 3 minutes.”
There are currently no products that detect the prone position or have the ability to reposition a patient quickly into the recovery sideways position.
Lee and his colleagues developed a smart system that can be embedded in a mattress that detects when someone is having a seizure, determines if that person is face down, and if so, safely stimulates and repositions them.
The mattress is made up of a series of programmable inflatable blocks or “cells” that have pressure, vibration, temperature, and humidity sensors embedded within. “Based on the pressure readings, we can figure out whether the patient is right side up, on their right side, on their left side, or face down,” said Lee.
If the person is face down, he or she can be repositioned within a matter of seconds. “Each of the cells can lift 1000 pounds,” he said. The mattress is “very comfortable,” said Lee, who has tried it out himself.
Eighteen normative control participants have been enrolled for development and training purposes. To date, 10 of these individuals, aged 18-53 years, weighing 100-182 lb, and with a height of 5 ft 2 in to 6 ft 1 in, underwent extensive formal testing on the prototype bed.
Researchers found the mattress responded quickly to different body positions and weights. “We were able to reposition everybody in around 20 seconds,” said Lee.
The overall accuracy of detecting the prone position was 96.8%. There were no cases of a supine or prone position being mistaken for each other.
Researchers are refining the algorithm to improve the accuracy for detecting the prone position and expect to have a completely functional prototype within a few years.
Big Step Forward
Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor, Division of Epilepsy, Harvard Beth Israel Deaconess Medical Center, Boston, said the study “is a big step forward in the race to provide an actionable tool to prevent SUDEP.”
The technology “appears to mostly be doing what it’s intended to do, with relatively minor technical errors being made,” he said.
However, it is not clear if this technology can truly save lives, said Goldenholz. “The data we have suggests that lying face down in bed after a seizure is correlated with SUDEP, but that does not mean that if we can simply flip people over, they for sure won’t die.”
Even if the new technology “works perfectly,” it’s still an open question, said Goldenholz. If it does save lives, “this will be a major breakthrough, and one that has been needed for a long time.”
However, even if it does not, he congratulates the team for trying to determine if reducing the prone position can help prevent SUDEP. He would like to see more “high-risk, high-reward” studies in the epilepsy field. “We are in so much need of new innovations.”
He said he was “personally very inspired” by this work. “People are dying from this terrible disease, and this team is building what they hope might save lives.”
The study was funded by the National Institutes of Health. The mattress is being developed by Soterya. Lee reported no equity in Soterya. Goldenholz reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
LOS ANGELES — says one of the experts involved in its development.
When used along with a seizure detection device, Jong Woo Lee, MD, PhD, associate professor of neurology, Harvard Medical School, and Brigham and Women’s Hospital, both in Boston, Massachusetts, estimates the smart mattress could cut SUDEP by more than 50%.
In addition, early results from an observational study are backing this up, he said.
The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
Most SUDEP Cases Found Face Down
SUDEP is the leading cause of death in children with epilepsy and in otherwise healthy adult patients with epilepsy. When his fifth patient died of SUDEP, Lee decided it was time to try to tackle the high mortality rate associated with these unexpected deaths. “I desperately wanted to help, ” he said.
About 70% of SUDEP occurs during sleep, and victims are found face down, or in the prone position, 90% of the time, said Lee.
“Of course, the best way to prevent SUDEP is not to have a seizure, but once you have a seizure and once you’re face down, your risk for death goes up by somewhere between 30 and 100 times,” he explained.
Lee was convinced SUDEP could be prevented by simple interventions that stimulate the patient and turn them over. He noted the incidence of sudden infant death syndrome, “which has similar characteristics” to SUDEP, has been reduced by up to 75% through campaigns that simply advise placing babies on their backs.
“Most of SUDEP happens because your arousal system is knocked out and you just don’t take the breath that you’re supposed to. Just the act of turning people over and vibrating the bed will stimulate them,” he said.
However, it’s crucial that this be done quickly, said Lee. “When you look at patients who died on video and see the EEGs, everybody took their last breath within 3 minutes.”
Because the window of opportunity is so short, “we think that seizure detection devices alone are not going to really be effective because you just can’t get there or react within those 3 minutes.”
There are currently no products that detect the prone position or have the ability to reposition a patient quickly into the recovery sideways position.
Lee and his colleagues developed a smart system that can be embedded in a mattress that detects when someone is having a seizure, determines if that person is face down, and if so, safely stimulates and repositions them.
The mattress is made up of a series of programmable inflatable blocks or “cells” that have pressure, vibration, temperature, and humidity sensors embedded within. “Based on the pressure readings, we can figure out whether the patient is right side up, on their right side, on their left side, or face down,” said Lee.
If the person is face down, he or she can be repositioned within a matter of seconds. “Each of the cells can lift 1000 pounds,” he said. The mattress is “very comfortable,” said Lee, who has tried it out himself.
Eighteen normative control participants have been enrolled for development and training purposes. To date, 10 of these individuals, aged 18-53 years, weighing 100-182 lb, and with a height of 5 ft 2 in to 6 ft 1 in, underwent extensive formal testing on the prototype bed.
Researchers found the mattress responded quickly to different body positions and weights. “We were able to reposition everybody in around 20 seconds,” said Lee.
The overall accuracy of detecting the prone position was 96.8%. There were no cases of a supine or prone position being mistaken for each other.
Researchers are refining the algorithm to improve the accuracy for detecting the prone position and expect to have a completely functional prototype within a few years.
Big Step Forward
Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor, Division of Epilepsy, Harvard Beth Israel Deaconess Medical Center, Boston, said the study “is a big step forward in the race to provide an actionable tool to prevent SUDEP.”
The technology “appears to mostly be doing what it’s intended to do, with relatively minor technical errors being made,” he said.
However, it is not clear if this technology can truly save lives, said Goldenholz. “The data we have suggests that lying face down in bed after a seizure is correlated with SUDEP, but that does not mean that if we can simply flip people over, they for sure won’t die.”
Even if the new technology “works perfectly,” it’s still an open question, said Goldenholz. If it does save lives, “this will be a major breakthrough, and one that has been needed for a long time.”
However, even if it does not, he congratulates the team for trying to determine if reducing the prone position can help prevent SUDEP. He would like to see more “high-risk, high-reward” studies in the epilepsy field. “We are in so much need of new innovations.”
He said he was “personally very inspired” by this work. “People are dying from this terrible disease, and this team is building what they hope might save lives.”
The study was funded by the National Institutes of Health. The mattress is being developed by Soterya. Lee reported no equity in Soterya. Goldenholz reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
LOS ANGELES — says one of the experts involved in its development.
When used along with a seizure detection device, Jong Woo Lee, MD, PhD, associate professor of neurology, Harvard Medical School, and Brigham and Women’s Hospital, both in Boston, Massachusetts, estimates the smart mattress could cut SUDEP by more than 50%.
In addition, early results from an observational study are backing this up, he said.
The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
Most SUDEP Cases Found Face Down
SUDEP is the leading cause of death in children with epilepsy and in otherwise healthy adult patients with epilepsy. When his fifth patient died of SUDEP, Lee decided it was time to try to tackle the high mortality rate associated with these unexpected deaths. “I desperately wanted to help, ” he said.
About 70% of SUDEP occurs during sleep, and victims are found face down, or in the prone position, 90% of the time, said Lee.
“Of course, the best way to prevent SUDEP is not to have a seizure, but once you have a seizure and once you’re face down, your risk for death goes up by somewhere between 30 and 100 times,” he explained.
Lee was convinced SUDEP could be prevented by simple interventions that stimulate the patient and turn them over. He noted the incidence of sudden infant death syndrome, “which has similar characteristics” to SUDEP, has been reduced by up to 75% through campaigns that simply advise placing babies on their backs.
“Most of SUDEP happens because your arousal system is knocked out and you just don’t take the breath that you’re supposed to. Just the act of turning people over and vibrating the bed will stimulate them,” he said.
However, it’s crucial that this be done quickly, said Lee. “When you look at patients who died on video and see the EEGs, everybody took their last breath within 3 minutes.”
Because the window of opportunity is so short, “we think that seizure detection devices alone are not going to really be effective because you just can’t get there or react within those 3 minutes.”
There are currently no products that detect the prone position or have the ability to reposition a patient quickly into the recovery sideways position.
Lee and his colleagues developed a smart system that can be embedded in a mattress that detects when someone is having a seizure, determines if that person is face down, and if so, safely stimulates and repositions them.
The mattress is made up of a series of programmable inflatable blocks or “cells” that have pressure, vibration, temperature, and humidity sensors embedded within. “Based on the pressure readings, we can figure out whether the patient is right side up, on their right side, on their left side, or face down,” said Lee.
If the person is face down, he or she can be repositioned within a matter of seconds. “Each of the cells can lift 1000 pounds,” he said. The mattress is “very comfortable,” said Lee, who has tried it out himself.
Eighteen normative control participants have been enrolled for development and training purposes. To date, 10 of these individuals, aged 18-53 years, weighing 100-182 lb, and with a height of 5 ft 2 in to 6 ft 1 in, underwent extensive formal testing on the prototype bed.
Researchers found the mattress responded quickly to different body positions and weights. “We were able to reposition everybody in around 20 seconds,” said Lee.
The overall accuracy of detecting the prone position was 96.8%. There were no cases of a supine or prone position being mistaken for each other.
Researchers are refining the algorithm to improve the accuracy for detecting the prone position and expect to have a completely functional prototype within a few years.
Big Step Forward
Commenting on the research, Daniel M. Goldenholz, MD, PhD, assistant professor, Division of Epilepsy, Harvard Beth Israel Deaconess Medical Center, Boston, said the study “is a big step forward in the race to provide an actionable tool to prevent SUDEP.”
The technology “appears to mostly be doing what it’s intended to do, with relatively minor technical errors being made,” he said.
However, it is not clear if this technology can truly save lives, said Goldenholz. “The data we have suggests that lying face down in bed after a seizure is correlated with SUDEP, but that does not mean that if we can simply flip people over, they for sure won’t die.”
Even if the new technology “works perfectly,” it’s still an open question, said Goldenholz. If it does save lives, “this will be a major breakthrough, and one that has been needed for a long time.”
However, even if it does not, he congratulates the team for trying to determine if reducing the prone position can help prevent SUDEP. He would like to see more “high-risk, high-reward” studies in the epilepsy field. “We are in so much need of new innovations.”
He said he was “personally very inspired” by this work. “People are dying from this terrible disease, and this team is building what they hope might save lives.”
The study was funded by the National Institutes of Health. The mattress is being developed by Soterya. Lee reported no equity in Soterya. Goldenholz reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM AES 2024
Sleep Apnea Linked to Heightened Mortality in Epilepsy
LOS ANGELES — according to a new analysis of over 2 million patient-years drawn from the Komodo Health Claims Database.
“A 10-year-old with uncontrolled epilepsy and central sleep apnea is about 200 times more likely to die than a general population 10-year-old. That’s comparable to a 10-year-old with {epilepsy and} congestive heart failure. Noncentral sleep apnea is comparable to being paralyzed. It’s a huge risk factor,” said poster presenter Dan Lloyd, advanced analytics lead at UCB, which sponsored the research.
The ordering of sleep apnea tests for patients with epilepsy is widely variable, according to Stefanie Dedeurwaerdere, PhD, who is the innovation and value creation lead at UCB. “Some doctors do that as a general practice, and some don’t. There’s no coherency in the way these studies are requested for epilepsy patients. We want to create some awareness around this topic,” she said, and added that treatment of sleep apnea may improve epileptic seizures.
The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
The study included mortality rates between January 2018 and December 2022, with a total of 2,355,410 patient-years and 968,993 patients, with an age distribution of 19.1% age 1 to less than 18 years, 23.7% age 18-35 years, and 57.2% age 36 years or older. Sleep apnea prevalences were 0.7% for central sleep apnea (CSA), 14.0% for obstructive sleep apnea (OSA), and 85.3% with no sleep apnea.
Among those aged 1-18 years, the standardized mortality ratio (SMR) for those with uncontrolled epilepsy was 27.7. For those with comorbid OSA, the SMR was 74.2, and for comorbid CSA, the SMR was 135.9. The association was less pronounced in older groups, dipping to 7.0, 11.3, and 19.5 in those aged 18-35 years, and 3.3, 3.1, and 2.8 among those aged 36 years or older.
Among the 1-18 age group, SMRs for other comorbidities included 132.3 for heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease.
Asked for comment, Gordon Buchanan, MD, PhD, welcomed the new work. “The results did not surprise me. I study sleep, epilepsy, and [sudden unexplained death in epilepsy (SUDEP)] in particular ... and every time I speak on these topics, someone asks me about risk of SUDEP in patients with sleep apnea. It’s great to finally have some data,” said Buchanan, a professor of neurology at the University of Iowa, Iowa City.
The authors found that patients undergoing continuous positive airway pressure (CPAP)/bi-level positive airway pressure therapy had a higher mortality risk than those not undergoing CPAP therapy but cautioned that uncontrolled confounders may be contributing to the effect.
Buchanan wondered if treatment with CPAP would be associated with a decreased mortality risk. “I think that would be interesting, but I know that, especially in children, it can be difficult to get them to remain compliant with CPAP. I think that would be interesting to know, if pushing harder to get the kids to comply with CPAP would reduce mortality,” he said.
The specific finding of heightened mortality associated with CSA is interesting, according to Buchanan. “We think of seizures propagating through the brain, maybe through direct synaptic connections or through spreading depolarization. So I think it would make sense that it would hit central regions that would then lead to sleep apnea.”
The relationship between OSA and epilepsy is likely complex. Epilepsy medications and special diets may influence body composition, which could in turn affect the risk for OSA, as could medications associated with psychiatric comorbidities, according to Buchanan.
The study is retrospective and based on claims data. It does not prove causation, and claims data do not fully capture mortality, which may lead to conservative SMR estimates. The researchers did not control for socioeconomic status, treatment status, and other comorbidities or conditions.
Lloyd and Dedeurwaerdere are employees of UCB, which sponsored the study. Buchanan had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
LOS ANGELES — according to a new analysis of over 2 million patient-years drawn from the Komodo Health Claims Database.
“A 10-year-old with uncontrolled epilepsy and central sleep apnea is about 200 times more likely to die than a general population 10-year-old. That’s comparable to a 10-year-old with {epilepsy and} congestive heart failure. Noncentral sleep apnea is comparable to being paralyzed. It’s a huge risk factor,” said poster presenter Dan Lloyd, advanced analytics lead at UCB, which sponsored the research.
The ordering of sleep apnea tests for patients with epilepsy is widely variable, according to Stefanie Dedeurwaerdere, PhD, who is the innovation and value creation lead at UCB. “Some doctors do that as a general practice, and some don’t. There’s no coherency in the way these studies are requested for epilepsy patients. We want to create some awareness around this topic,” she said, and added that treatment of sleep apnea may improve epileptic seizures.
The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
The study included mortality rates between January 2018 and December 2022, with a total of 2,355,410 patient-years and 968,993 patients, with an age distribution of 19.1% age 1 to less than 18 years, 23.7% age 18-35 years, and 57.2% age 36 years or older. Sleep apnea prevalences were 0.7% for central sleep apnea (CSA), 14.0% for obstructive sleep apnea (OSA), and 85.3% with no sleep apnea.
Among those aged 1-18 years, the standardized mortality ratio (SMR) for those with uncontrolled epilepsy was 27.7. For those with comorbid OSA, the SMR was 74.2, and for comorbid CSA, the SMR was 135.9. The association was less pronounced in older groups, dipping to 7.0, 11.3, and 19.5 in those aged 18-35 years, and 3.3, 3.1, and 2.8 among those aged 36 years or older.
Among the 1-18 age group, SMRs for other comorbidities included 132.3 for heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease.
Asked for comment, Gordon Buchanan, MD, PhD, welcomed the new work. “The results did not surprise me. I study sleep, epilepsy, and [sudden unexplained death in epilepsy (SUDEP)] in particular ... and every time I speak on these topics, someone asks me about risk of SUDEP in patients with sleep apnea. It’s great to finally have some data,” said Buchanan, a professor of neurology at the University of Iowa, Iowa City.
The authors found that patients undergoing continuous positive airway pressure (CPAP)/bi-level positive airway pressure therapy had a higher mortality risk than those not undergoing CPAP therapy but cautioned that uncontrolled confounders may be contributing to the effect.
Buchanan wondered if treatment with CPAP would be associated with a decreased mortality risk. “I think that would be interesting, but I know that, especially in children, it can be difficult to get them to remain compliant with CPAP. I think that would be interesting to know, if pushing harder to get the kids to comply with CPAP would reduce mortality,” he said.
The specific finding of heightened mortality associated with CSA is interesting, according to Buchanan. “We think of seizures propagating through the brain, maybe through direct synaptic connections or through spreading depolarization. So I think it would make sense that it would hit central regions that would then lead to sleep apnea.”
The relationship between OSA and epilepsy is likely complex. Epilepsy medications and special diets may influence body composition, which could in turn affect the risk for OSA, as could medications associated with psychiatric comorbidities, according to Buchanan.
The study is retrospective and based on claims data. It does not prove causation, and claims data do not fully capture mortality, which may lead to conservative SMR estimates. The researchers did not control for socioeconomic status, treatment status, and other comorbidities or conditions.
Lloyd and Dedeurwaerdere are employees of UCB, which sponsored the study. Buchanan had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
LOS ANGELES — according to a new analysis of over 2 million patient-years drawn from the Komodo Health Claims Database.
“A 10-year-old with uncontrolled epilepsy and central sleep apnea is about 200 times more likely to die than a general population 10-year-old. That’s comparable to a 10-year-old with {epilepsy and} congestive heart failure. Noncentral sleep apnea is comparable to being paralyzed. It’s a huge risk factor,” said poster presenter Dan Lloyd, advanced analytics lead at UCB, which sponsored the research.
The ordering of sleep apnea tests for patients with epilepsy is widely variable, according to Stefanie Dedeurwaerdere, PhD, who is the innovation and value creation lead at UCB. “Some doctors do that as a general practice, and some don’t. There’s no coherency in the way these studies are requested for epilepsy patients. We want to create some awareness around this topic,” she said, and added that treatment of sleep apnea may improve epileptic seizures.
The findings were presented at the American Epilepsy Society (AES) 78th Annual Meeting 2024.
The study included mortality rates between January 2018 and December 2022, with a total of 2,355,410 patient-years and 968,993 patients, with an age distribution of 19.1% age 1 to less than 18 years, 23.7% age 18-35 years, and 57.2% age 36 years or older. Sleep apnea prevalences were 0.7% for central sleep apnea (CSA), 14.0% for obstructive sleep apnea (OSA), and 85.3% with no sleep apnea.
Among those aged 1-18 years, the standardized mortality ratio (SMR) for those with uncontrolled epilepsy was 27.7. For those with comorbid OSA, the SMR was 74.2, and for comorbid CSA, the SMR was 135.9. The association was less pronounced in older groups, dipping to 7.0, 11.3, and 19.5 in those aged 18-35 years, and 3.3, 3.1, and 2.8 among those aged 36 years or older.
Among the 1-18 age group, SMRs for other comorbidities included 132.3 for heart failure, 74.9 for hemiplegia/paraplegia, 55.3 for cerebrovascular disease, and 44.6 for chronic pulmonary disease.
Asked for comment, Gordon Buchanan, MD, PhD, welcomed the new work. “The results did not surprise me. I study sleep, epilepsy, and [sudden unexplained death in epilepsy (SUDEP)] in particular ... and every time I speak on these topics, someone asks me about risk of SUDEP in patients with sleep apnea. It’s great to finally have some data,” said Buchanan, a professor of neurology at the University of Iowa, Iowa City.
The authors found that patients undergoing continuous positive airway pressure (CPAP)/bi-level positive airway pressure therapy had a higher mortality risk than those not undergoing CPAP therapy but cautioned that uncontrolled confounders may be contributing to the effect.
Buchanan wondered if treatment with CPAP would be associated with a decreased mortality risk. “I think that would be interesting, but I know that, especially in children, it can be difficult to get them to remain compliant with CPAP. I think that would be interesting to know, if pushing harder to get the kids to comply with CPAP would reduce mortality,” he said.
The specific finding of heightened mortality associated with CSA is interesting, according to Buchanan. “We think of seizures propagating through the brain, maybe through direct synaptic connections or through spreading depolarization. So I think it would make sense that it would hit central regions that would then lead to sleep apnea.”
The relationship between OSA and epilepsy is likely complex. Epilepsy medications and special diets may influence body composition, which could in turn affect the risk for OSA, as could medications associated with psychiatric comorbidities, according to Buchanan.
The study is retrospective and based on claims data. It does not prove causation, and claims data do not fully capture mortality, which may lead to conservative SMR estimates. The researchers did not control for socioeconomic status, treatment status, and other comorbidities or conditions.
Lloyd and Dedeurwaerdere are employees of UCB, which sponsored the study. Buchanan had no relevant financial disclosures.
A version of this article appeared on Medscape.com.
FROM AES 2024
Rise in Psychotherapy Use Exposes Access Inequities
Outpatient psychotherapy use in the United States rose sharply between 2018 and 2021, an increase that was driven primarily by young, urban professionals with higher family incomes, new data exposed significant disparities in access to this treatment type.
Results of a large population-based repeated cross-sectional study revealed that psychotherapy use increased significantly faster for women vs men, younger individuals vs their older counterparts, college graduates than those without a high school diploma, and privately insured vs publicly insured individuals.
Overall, psychotherapy use increased significantly faster among several socioeconomically advantaged groups, and inequalities were evident in teletherapy access. These trends and patterns highlight a need for clinical interventions and healthcare policies to broaden access to psychotherapy, including teletherapy, the authors noted.
“While psychotherapy access has expanded in the US, there’s concern that recent gains may not be equally distributed, despite or maybe because of the growth of teletherapy,” study author Mark Olfson, MD, MPH, Department of Psychiatry, Mailman School of Public Health, Columbia University, New York City, said in a press release.
“This increase in psychotherapy use, driven by the rise of teletherapy, has largely benefited socioeconomically advantaged adults with mild to moderate distress,” he added.
The findings were published online in JAMA Psychiatry.
Psychotherapy Uptick
Psychotherapy is among the most widely used methods for delivering mental health care in the United States. A recent study conducted by Olfson and colleagues showed that the percentage of US adults receiving psychotherapy increased from 6.5% in 2018 to 8.5% in 2021. However, it was unclear how this overall increase varied across different sociodemographic groups or levels of psychological distress.
Analyzing population-level trends in psychotherapy use can identify sociodemographic groups with declining access to services, providing valuable insights for developing initiatives to improve accessibility, the investigators noted.
To evaluate national trends in psychotherapy use, the researchers analyzed data from the 2018-2021 Medical Expenditure Panel Survey (MEPS). These are yearly surveys representing noninstitutionalized adults across the United States.
The study included 89,619 adults. Of these, 51.5% were women, nearly half were aged 35-64 years, and 62.2% were White individuals. The study used a repeated cross-sectional design with new, nationally representative samples of about 22,000 participants each year.
The investigators tracked the overall increase in psychotherapy use, especially among groups at higher risk for untreated mental health conditions. They also examined how video-based therapy (teletherapy) was being used, paying particular attention to differences in access among various demographic groups and levels of psychological distress, given ongoing concerns about equity in telehealth access.
Psychological distress was measured using the Kessler-6 scale, with scores ≥ 13 defining serious psychological distress, 1-12 defining mild to moderate distress, and 0 defining no distress.
Psychotherapy use increased across all racial and ethnic groups, with rates rising among Black (5.4% to 7.1%), Hispanic (4.1% to 5.8%), White (7.5% to 9.8%), and other, non-Hispanic (4.8% to 6.6%) individuals.
Participants with mild to moderate distress experienced the greatest increases in psychotherapy use (8.6% to 11.2%, respectively).
After adjusting for age, sex, and level of psychological distress, investigators found that psychotherapy use increased to a greater degree among women (7.7% to 10.5%) vs men (5.2% to 6.3%), younger adults aged 18-34 years (8% to 11.9%) vs adults aged 65 years or older (3.6% to 4.6%), and college graduates (7.6% to 11.4%) than those without a high school diploma (5.5% to 7%).
A National Priority
Adults with higher incomes — defined as two to four times the federal poverty level — had greater increases in psychotherapy use (5.7% to 8.2%) than those below the poverty level (9.7% to 10%).
Unsurprisingly, privately insured individuals saw more significant increases (6.1% to 8.9%) than publicly insured individuals (8.8% to 8.8%). Also, there was a larger increase in psychotherapy use among employed individuals (5.7% to 8.9%) than among unemployed individuals (10.8% to 10.5%).
In addition, there was a significantly greater increase in psychotherapy use among urban residents (6.5% to 8.7%), whereas it declined among rural residents (6.4% to 5.9%).
Data on teletherapy use from 2021 revealed that 39.9% of adults receiving psychotherapy had one or more teletherapy visits.
Teletherapy use was higher among younger adults, women, college-educated individuals, those with higher incomes, those with private insurance, and those who lived in urban areas.
The authors noted that while teletherapy is intended to remove transportation and time barriers and was widely adopted during the pandemic, the findings show that those who were older, less educated, and with lower incomes were less likely to use it.
Notably, urban residents were more than twice as likely to use teletherapy than rural residents. Prior to the COVID-19 pandemic, teletherapy was viewed as a potential solution for individuals living in rural areas facing a shortage of mental health professionals, but study results showed that “teletherapy does not appear to have addressed this public health challenge,” the investigators wrote.
“The trends we are seeing underscore the need for targeted interventions and health policies that expand psychotherapy access to underserved groups,” said Olfson.
“Ensuring that individuals in psychological distress can access care is a national priority. Addressing technical and financial barriers to teletherapy could help bridge the gap in access and promote equity in mental health care,” he added.
Study limitations included a possible underreporting of psychotherapy use by participants. In addition, MEPS does not include nursing home residents, incarcerated, and unhoused individuals.
Study funding was not disclosed. Olfson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Outpatient psychotherapy use in the United States rose sharply between 2018 and 2021, an increase that was driven primarily by young, urban professionals with higher family incomes, new data exposed significant disparities in access to this treatment type.
Results of a large population-based repeated cross-sectional study revealed that psychotherapy use increased significantly faster for women vs men, younger individuals vs their older counterparts, college graduates than those without a high school diploma, and privately insured vs publicly insured individuals.
Overall, psychotherapy use increased significantly faster among several socioeconomically advantaged groups, and inequalities were evident in teletherapy access. These trends and patterns highlight a need for clinical interventions and healthcare policies to broaden access to psychotherapy, including teletherapy, the authors noted.
“While psychotherapy access has expanded in the US, there’s concern that recent gains may not be equally distributed, despite or maybe because of the growth of teletherapy,” study author Mark Olfson, MD, MPH, Department of Psychiatry, Mailman School of Public Health, Columbia University, New York City, said in a press release.
“This increase in psychotherapy use, driven by the rise of teletherapy, has largely benefited socioeconomically advantaged adults with mild to moderate distress,” he added.
The findings were published online in JAMA Psychiatry.
Psychotherapy Uptick
Psychotherapy is among the most widely used methods for delivering mental health care in the United States. A recent study conducted by Olfson and colleagues showed that the percentage of US adults receiving psychotherapy increased from 6.5% in 2018 to 8.5% in 2021. However, it was unclear how this overall increase varied across different sociodemographic groups or levels of psychological distress.
Analyzing population-level trends in psychotherapy use can identify sociodemographic groups with declining access to services, providing valuable insights for developing initiatives to improve accessibility, the investigators noted.
To evaluate national trends in psychotherapy use, the researchers analyzed data from the 2018-2021 Medical Expenditure Panel Survey (MEPS). These are yearly surveys representing noninstitutionalized adults across the United States.
The study included 89,619 adults. Of these, 51.5% were women, nearly half were aged 35-64 years, and 62.2% were White individuals. The study used a repeated cross-sectional design with new, nationally representative samples of about 22,000 participants each year.
The investigators tracked the overall increase in psychotherapy use, especially among groups at higher risk for untreated mental health conditions. They also examined how video-based therapy (teletherapy) was being used, paying particular attention to differences in access among various demographic groups and levels of psychological distress, given ongoing concerns about equity in telehealth access.
Psychological distress was measured using the Kessler-6 scale, with scores ≥ 13 defining serious psychological distress, 1-12 defining mild to moderate distress, and 0 defining no distress.
Psychotherapy use increased across all racial and ethnic groups, with rates rising among Black (5.4% to 7.1%), Hispanic (4.1% to 5.8%), White (7.5% to 9.8%), and other, non-Hispanic (4.8% to 6.6%) individuals.
Participants with mild to moderate distress experienced the greatest increases in psychotherapy use (8.6% to 11.2%, respectively).
After adjusting for age, sex, and level of psychological distress, investigators found that psychotherapy use increased to a greater degree among women (7.7% to 10.5%) vs men (5.2% to 6.3%), younger adults aged 18-34 years (8% to 11.9%) vs adults aged 65 years or older (3.6% to 4.6%), and college graduates (7.6% to 11.4%) than those without a high school diploma (5.5% to 7%).
A National Priority
Adults with higher incomes — defined as two to four times the federal poverty level — had greater increases in psychotherapy use (5.7% to 8.2%) than those below the poverty level (9.7% to 10%).
Unsurprisingly, privately insured individuals saw more significant increases (6.1% to 8.9%) than publicly insured individuals (8.8% to 8.8%). Also, there was a larger increase in psychotherapy use among employed individuals (5.7% to 8.9%) than among unemployed individuals (10.8% to 10.5%).
In addition, there was a significantly greater increase in psychotherapy use among urban residents (6.5% to 8.7%), whereas it declined among rural residents (6.4% to 5.9%).
Data on teletherapy use from 2021 revealed that 39.9% of adults receiving psychotherapy had one or more teletherapy visits.
Teletherapy use was higher among younger adults, women, college-educated individuals, those with higher incomes, those with private insurance, and those who lived in urban areas.
The authors noted that while teletherapy is intended to remove transportation and time barriers and was widely adopted during the pandemic, the findings show that those who were older, less educated, and with lower incomes were less likely to use it.
Notably, urban residents were more than twice as likely to use teletherapy than rural residents. Prior to the COVID-19 pandemic, teletherapy was viewed as a potential solution for individuals living in rural areas facing a shortage of mental health professionals, but study results showed that “teletherapy does not appear to have addressed this public health challenge,” the investigators wrote.
“The trends we are seeing underscore the need for targeted interventions and health policies that expand psychotherapy access to underserved groups,” said Olfson.
“Ensuring that individuals in psychological distress can access care is a national priority. Addressing technical and financial barriers to teletherapy could help bridge the gap in access and promote equity in mental health care,” he added.
Study limitations included a possible underreporting of psychotherapy use by participants. In addition, MEPS does not include nursing home residents, incarcerated, and unhoused individuals.
Study funding was not disclosed. Olfson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Outpatient psychotherapy use in the United States rose sharply between 2018 and 2021, an increase that was driven primarily by young, urban professionals with higher family incomes, new data exposed significant disparities in access to this treatment type.
Results of a large population-based repeated cross-sectional study revealed that psychotherapy use increased significantly faster for women vs men, younger individuals vs their older counterparts, college graduates than those without a high school diploma, and privately insured vs publicly insured individuals.
Overall, psychotherapy use increased significantly faster among several socioeconomically advantaged groups, and inequalities were evident in teletherapy access. These trends and patterns highlight a need for clinical interventions and healthcare policies to broaden access to psychotherapy, including teletherapy, the authors noted.
“While psychotherapy access has expanded in the US, there’s concern that recent gains may not be equally distributed, despite or maybe because of the growth of teletherapy,” study author Mark Olfson, MD, MPH, Department of Psychiatry, Mailman School of Public Health, Columbia University, New York City, said in a press release.
“This increase in psychotherapy use, driven by the rise of teletherapy, has largely benefited socioeconomically advantaged adults with mild to moderate distress,” he added.
The findings were published online in JAMA Psychiatry.
Psychotherapy Uptick
Psychotherapy is among the most widely used methods for delivering mental health care in the United States. A recent study conducted by Olfson and colleagues showed that the percentage of US adults receiving psychotherapy increased from 6.5% in 2018 to 8.5% in 2021. However, it was unclear how this overall increase varied across different sociodemographic groups or levels of psychological distress.
Analyzing population-level trends in psychotherapy use can identify sociodemographic groups with declining access to services, providing valuable insights for developing initiatives to improve accessibility, the investigators noted.
To evaluate national trends in psychotherapy use, the researchers analyzed data from the 2018-2021 Medical Expenditure Panel Survey (MEPS). These are yearly surveys representing noninstitutionalized adults across the United States.
The study included 89,619 adults. Of these, 51.5% were women, nearly half were aged 35-64 years, and 62.2% were White individuals. The study used a repeated cross-sectional design with new, nationally representative samples of about 22,000 participants each year.
The investigators tracked the overall increase in psychotherapy use, especially among groups at higher risk for untreated mental health conditions. They also examined how video-based therapy (teletherapy) was being used, paying particular attention to differences in access among various demographic groups and levels of psychological distress, given ongoing concerns about equity in telehealth access.
Psychological distress was measured using the Kessler-6 scale, with scores ≥ 13 defining serious psychological distress, 1-12 defining mild to moderate distress, and 0 defining no distress.
Psychotherapy use increased across all racial and ethnic groups, with rates rising among Black (5.4% to 7.1%), Hispanic (4.1% to 5.8%), White (7.5% to 9.8%), and other, non-Hispanic (4.8% to 6.6%) individuals.
Participants with mild to moderate distress experienced the greatest increases in psychotherapy use (8.6% to 11.2%, respectively).
After adjusting for age, sex, and level of psychological distress, investigators found that psychotherapy use increased to a greater degree among women (7.7% to 10.5%) vs men (5.2% to 6.3%), younger adults aged 18-34 years (8% to 11.9%) vs adults aged 65 years or older (3.6% to 4.6%), and college graduates (7.6% to 11.4%) than those without a high school diploma (5.5% to 7%).
A National Priority
Adults with higher incomes — defined as two to four times the federal poverty level — had greater increases in psychotherapy use (5.7% to 8.2%) than those below the poverty level (9.7% to 10%).
Unsurprisingly, privately insured individuals saw more significant increases (6.1% to 8.9%) than publicly insured individuals (8.8% to 8.8%). Also, there was a larger increase in psychotherapy use among employed individuals (5.7% to 8.9%) than among unemployed individuals (10.8% to 10.5%).
In addition, there was a significantly greater increase in psychotherapy use among urban residents (6.5% to 8.7%), whereas it declined among rural residents (6.4% to 5.9%).
Data on teletherapy use from 2021 revealed that 39.9% of adults receiving psychotherapy had one or more teletherapy visits.
Teletherapy use was higher among younger adults, women, college-educated individuals, those with higher incomes, those with private insurance, and those who lived in urban areas.
The authors noted that while teletherapy is intended to remove transportation and time barriers and was widely adopted during the pandemic, the findings show that those who were older, less educated, and with lower incomes were less likely to use it.
Notably, urban residents were more than twice as likely to use teletherapy than rural residents. Prior to the COVID-19 pandemic, teletherapy was viewed as a potential solution for individuals living in rural areas facing a shortage of mental health professionals, but study results showed that “teletherapy does not appear to have addressed this public health challenge,” the investigators wrote.
“The trends we are seeing underscore the need for targeted interventions and health policies that expand psychotherapy access to underserved groups,” said Olfson.
“Ensuring that individuals in psychological distress can access care is a national priority. Addressing technical and financial barriers to teletherapy could help bridge the gap in access and promote equity in mental health care,” he added.
Study limitations included a possible underreporting of psychotherapy use by participants. In addition, MEPS does not include nursing home residents, incarcerated, and unhoused individuals.
Study funding was not disclosed. Olfson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Skin Stress Biomarker May Predict Nerve Damage in Early T2D
TOPLINE:
Increased cutaneous carbonyl stress is linked to slower nerve conduction in patients with metabolically well-controlled, recent-onset type 2 diabetes (T2D) and can predict the development of neuropathic deficits over 5 years.
METHODOLOGY:
- Accumulation of advanced glycation end products (AGEs), which results from endogenous carbonyl stress, may be a potential target for preventing and treating the diabetic sensorimotor polyneuropathy (DSPN) that is a common complication of T2D.
- Researchers investigated novel cutaneous biomarkers for the development and progression of DSPN in 160 individuals with recent-onset T2D (diagnosed within 12 months or less) and 144 individuals with normal glucose tolerance, all recruited consecutively from the German Diabetes Study baseline cohort.
- Peripheral nerve function was assessed through nerve conduction studies, quantitative sensory testing, and clinical neuropathy scores.
- Skin biopsies were used to analyze intraepidermal nerve fiber density, endothelial integrity, cutaneous oxidative stress markers, and cutaneous carbonyl stress markers, including AGE autofluorescence and argpyrimidine area.
- Skin autofluorescence was measured noninvasively using an AGE reader device.
- A subgroup of 80 patients with T2D were reassessed after 5 years to evaluate the progression of neurophysiological deficits.
TAKEAWAY:
- Patients with recent-onset T2D had greater AGE autofluorescence and argpyrimidine area (P ≤ .05 for both) and lower nerve fiber density (P ≤ .05) than individuals with normal glucose tolerance.
- In patients with T2D, AGE autofluorescence was inversely associated with nerve conduction (P = .0002, P = .002, and P = .001 for peroneal motor, median motor, and sural sensory nerve conduction velocity, respectively) and positively associated with AGE reader measurements (P < .05); no such associations were observed in those with normal glucose tolerance.
- In the prospective T2D cohort, associations were noted between cutaneous markers for AGEs and endothelial cells at baseline and changes in nerve function indices over a 5-year period.
IN PRACTICE:
“Prospective analyses revealed some predictive value of cutaneous AGEs and lower endothelial integrity for declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN, representing a potential therapeutic target,” the authors wrote.
SOURCE:
The study was led by Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. It was published online in Diabetes Care.
LIMITATIONS:
The observational design of the study limited the ability to draw causal conclusions. The groups were not matched for age or body mass index. Various mechanisms related to DSPN were analyzed; however, specific pathways of AGEs were not studied in detail. The relatively low number of individuals with clinically manifested DSPN limited the exploration of different stages of the condition.
DISCLOSURES:
The study was supported by a German Center for Diabetes Research grant. The German Diabetes Study was supported by the German Diabetes Center funded by the German Federal Ministry of Health (Berlin), the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research e.V. No relevant conflicts of interest were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Increased cutaneous carbonyl stress is linked to slower nerve conduction in patients with metabolically well-controlled, recent-onset type 2 diabetes (T2D) and can predict the development of neuropathic deficits over 5 years.
METHODOLOGY:
- Accumulation of advanced glycation end products (AGEs), which results from endogenous carbonyl stress, may be a potential target for preventing and treating the diabetic sensorimotor polyneuropathy (DSPN) that is a common complication of T2D.
- Researchers investigated novel cutaneous biomarkers for the development and progression of DSPN in 160 individuals with recent-onset T2D (diagnosed within 12 months or less) and 144 individuals with normal glucose tolerance, all recruited consecutively from the German Diabetes Study baseline cohort.
- Peripheral nerve function was assessed through nerve conduction studies, quantitative sensory testing, and clinical neuropathy scores.
- Skin biopsies were used to analyze intraepidermal nerve fiber density, endothelial integrity, cutaneous oxidative stress markers, and cutaneous carbonyl stress markers, including AGE autofluorescence and argpyrimidine area.
- Skin autofluorescence was measured noninvasively using an AGE reader device.
- A subgroup of 80 patients with T2D were reassessed after 5 years to evaluate the progression of neurophysiological deficits.
TAKEAWAY:
- Patients with recent-onset T2D had greater AGE autofluorescence and argpyrimidine area (P ≤ .05 for both) and lower nerve fiber density (P ≤ .05) than individuals with normal glucose tolerance.
- In patients with T2D, AGE autofluorescence was inversely associated with nerve conduction (P = .0002, P = .002, and P = .001 for peroneal motor, median motor, and sural sensory nerve conduction velocity, respectively) and positively associated with AGE reader measurements (P < .05); no such associations were observed in those with normal glucose tolerance.
- In the prospective T2D cohort, associations were noted between cutaneous markers for AGEs and endothelial cells at baseline and changes in nerve function indices over a 5-year period.
IN PRACTICE:
“Prospective analyses revealed some predictive value of cutaneous AGEs and lower endothelial integrity for declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN, representing a potential therapeutic target,” the authors wrote.
SOURCE:
The study was led by Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. It was published online in Diabetes Care.
LIMITATIONS:
The observational design of the study limited the ability to draw causal conclusions. The groups were not matched for age or body mass index. Various mechanisms related to DSPN were analyzed; however, specific pathways of AGEs were not studied in detail. The relatively low number of individuals with clinically manifested DSPN limited the exploration of different stages of the condition.
DISCLOSURES:
The study was supported by a German Center for Diabetes Research grant. The German Diabetes Study was supported by the German Diabetes Center funded by the German Federal Ministry of Health (Berlin), the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research e.V. No relevant conflicts of interest were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Increased cutaneous carbonyl stress is linked to slower nerve conduction in patients with metabolically well-controlled, recent-onset type 2 diabetes (T2D) and can predict the development of neuropathic deficits over 5 years.
METHODOLOGY:
- Accumulation of advanced glycation end products (AGEs), which results from endogenous carbonyl stress, may be a potential target for preventing and treating the diabetic sensorimotor polyneuropathy (DSPN) that is a common complication of T2D.
- Researchers investigated novel cutaneous biomarkers for the development and progression of DSPN in 160 individuals with recent-onset T2D (diagnosed within 12 months or less) and 144 individuals with normal glucose tolerance, all recruited consecutively from the German Diabetes Study baseline cohort.
- Peripheral nerve function was assessed through nerve conduction studies, quantitative sensory testing, and clinical neuropathy scores.
- Skin biopsies were used to analyze intraepidermal nerve fiber density, endothelial integrity, cutaneous oxidative stress markers, and cutaneous carbonyl stress markers, including AGE autofluorescence and argpyrimidine area.
- Skin autofluorescence was measured noninvasively using an AGE reader device.
- A subgroup of 80 patients with T2D were reassessed after 5 years to evaluate the progression of neurophysiological deficits.
TAKEAWAY:
- Patients with recent-onset T2D had greater AGE autofluorescence and argpyrimidine area (P ≤ .05 for both) and lower nerve fiber density (P ≤ .05) than individuals with normal glucose tolerance.
- In patients with T2D, AGE autofluorescence was inversely associated with nerve conduction (P = .0002, P = .002, and P = .001 for peroneal motor, median motor, and sural sensory nerve conduction velocity, respectively) and positively associated with AGE reader measurements (P < .05); no such associations were observed in those with normal glucose tolerance.
- In the prospective T2D cohort, associations were noted between cutaneous markers for AGEs and endothelial cells at baseline and changes in nerve function indices over a 5-year period.
IN PRACTICE:
“Prospective analyses revealed some predictive value of cutaneous AGEs and lower endothelial integrity for declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN, representing a potential therapeutic target,” the authors wrote.
SOURCE:
The study was led by Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. It was published online in Diabetes Care.
LIMITATIONS:
The observational design of the study limited the ability to draw causal conclusions. The groups were not matched for age or body mass index. Various mechanisms related to DSPN were analyzed; however, specific pathways of AGEs were not studied in detail. The relatively low number of individuals with clinically manifested DSPN limited the exploration of different stages of the condition.
DISCLOSURES:
The study was supported by a German Center for Diabetes Research grant. The German Diabetes Study was supported by the German Diabetes Center funded by the German Federal Ministry of Health (Berlin), the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research e.V. No relevant conflicts of interest were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Congress and VA Aim to Improve Health Care Access for Rural Veterans
Veterans living in rural areas are often too far away from health care institutions to easily travel to their appointments. Even if they can drive, the cost of gas and other related travel expenses may be too much for some. Telehealth was meant to help relieve that problem, but poor internet access can mitigate its convenience and accessibility for those patients. Two proposals offer solutions.
In February, Sens. Jon Ossoff (D-GA), Susan Collins (R-ME), and John Thune (R-SD) introduced the Rural Veterans Transportation to Care Act, a bill that would expand eligibility to the US Department of Veterans Affairs (VA) Highly Rural Transportation Grants, a program currently only available to counties with < 7 people per square mile.
“As I’ve sat down with veterans in rural areas across Georgia, one of their key concerns is lack of transportation,” Sen. Ossoff said. “That’s why I’m introducing this bipartisan bill to ensure veterans have more access to transportation services that can bring them to VA clinics and medical centers to get the care they need.”
Amanda Flener and her husband, John, a veteran wounded while serving in Iraq, were driving as long as 3 hours from Fitzgerald, Georgia (population 8900) to attend his medical appointments. In the last 2 years, Flener told the Daily Yonder she had put nearly 72,000 miles on her vehicle. Following hurricane Helene, she said, "We had been driving 30 miles just to get gas to power our generator … and we were fortunate to be able to do that.”
Telehealth appointments can help fill coverage gaps, Flener said. But even while paying for the most expensive internet plan available in her county, the signal isn't always strong enough. Telehealth care is "progress, for sure," Flener said. "So, we pay for the best Wi-Fi we can get in our area, but it isn't always reliable enough to take the video calls from the VA."
As a result, veterans and their caregivers could benefit not only from the bipartisan transportation proposal, but also from a decision announced in November. The VA is proposing to eliminate copayments for all VA telehealth services and establish a grant program to fund designated VA telehealth access points in non-VA facilities, with a focus on rural and medically underserved communities.
The program, called Accessing Telehealth through Local Area Stations (ATLAS), would provide funding to organizations — including nonprofits and private businesses — to offer veterans comfortable, private spaces equipped with high-speed internet access and the technology to remotely meet with VA clinicians. Grants would also provide designated funding to train on-site personnel to support the program.
These proposed changes would advance the VA’s and the Biden-Harris Administration’s ongoing efforts to lower costs and expand access to care for veterans. They also could make a life-changing difference for the 2.7 million rural veterans enrolled in VA health care.
According to a 2024 RAND study, just under half of military and veteran caregivers live in a county without a VA facility, and nearly half live in a primary care physician shortage area. For military/veteran caregivers in particular, the survey found, reduced access to support related to the more complicated care some patients require, greater distances to reach opportunities (eg, retail, economic, or social), and even differences in Wi-Fi/broadband internet access may create “unique needs.” The survey found that 24% of rural military/veteran caregivers did not have reliable broadband internet.
“Waiving copays for telehealth services and launching this grant program are both major steps forward in ensuring veterans can access health care where and when they need it,” said VA Secretary Denis McDonough. “VA is the best and most affordable care in America for veterans — with these steps, we can make it easier for veterans to access their earned VA health care.”
The rulemaking can be viewed in the Federal Register under public inspection, and is open for comment. The VA anticipates a notice of funding opportunity for this grant program following publication of the final rule.
Veterans living in rural areas are often too far away from health care institutions to easily travel to their appointments. Even if they can drive, the cost of gas and other related travel expenses may be too much for some. Telehealth was meant to help relieve that problem, but poor internet access can mitigate its convenience and accessibility for those patients. Two proposals offer solutions.
In February, Sens. Jon Ossoff (D-GA), Susan Collins (R-ME), and John Thune (R-SD) introduced the Rural Veterans Transportation to Care Act, a bill that would expand eligibility to the US Department of Veterans Affairs (VA) Highly Rural Transportation Grants, a program currently only available to counties with < 7 people per square mile.
“As I’ve sat down with veterans in rural areas across Georgia, one of their key concerns is lack of transportation,” Sen. Ossoff said. “That’s why I’m introducing this bipartisan bill to ensure veterans have more access to transportation services that can bring them to VA clinics and medical centers to get the care they need.”
Amanda Flener and her husband, John, a veteran wounded while serving in Iraq, were driving as long as 3 hours from Fitzgerald, Georgia (population 8900) to attend his medical appointments. In the last 2 years, Flener told the Daily Yonder she had put nearly 72,000 miles on her vehicle. Following hurricane Helene, she said, "We had been driving 30 miles just to get gas to power our generator … and we were fortunate to be able to do that.”
Telehealth appointments can help fill coverage gaps, Flener said. But even while paying for the most expensive internet plan available in her county, the signal isn't always strong enough. Telehealth care is "progress, for sure," Flener said. "So, we pay for the best Wi-Fi we can get in our area, but it isn't always reliable enough to take the video calls from the VA."
As a result, veterans and their caregivers could benefit not only from the bipartisan transportation proposal, but also from a decision announced in November. The VA is proposing to eliminate copayments for all VA telehealth services and establish a grant program to fund designated VA telehealth access points in non-VA facilities, with a focus on rural and medically underserved communities.
The program, called Accessing Telehealth through Local Area Stations (ATLAS), would provide funding to organizations — including nonprofits and private businesses — to offer veterans comfortable, private spaces equipped with high-speed internet access and the technology to remotely meet with VA clinicians. Grants would also provide designated funding to train on-site personnel to support the program.
These proposed changes would advance the VA’s and the Biden-Harris Administration’s ongoing efforts to lower costs and expand access to care for veterans. They also could make a life-changing difference for the 2.7 million rural veterans enrolled in VA health care.
According to a 2024 RAND study, just under half of military and veteran caregivers live in a county without a VA facility, and nearly half live in a primary care physician shortage area. For military/veteran caregivers in particular, the survey found, reduced access to support related to the more complicated care some patients require, greater distances to reach opportunities (eg, retail, economic, or social), and even differences in Wi-Fi/broadband internet access may create “unique needs.” The survey found that 24% of rural military/veteran caregivers did not have reliable broadband internet.
“Waiving copays for telehealth services and launching this grant program are both major steps forward in ensuring veterans can access health care where and when they need it,” said VA Secretary Denis McDonough. “VA is the best and most affordable care in America for veterans — with these steps, we can make it easier for veterans to access their earned VA health care.”
The rulemaking can be viewed in the Federal Register under public inspection, and is open for comment. The VA anticipates a notice of funding opportunity for this grant program following publication of the final rule.
Veterans living in rural areas are often too far away from health care institutions to easily travel to their appointments. Even if they can drive, the cost of gas and other related travel expenses may be too much for some. Telehealth was meant to help relieve that problem, but poor internet access can mitigate its convenience and accessibility for those patients. Two proposals offer solutions.
In February, Sens. Jon Ossoff (D-GA), Susan Collins (R-ME), and John Thune (R-SD) introduced the Rural Veterans Transportation to Care Act, a bill that would expand eligibility to the US Department of Veterans Affairs (VA) Highly Rural Transportation Grants, a program currently only available to counties with < 7 people per square mile.
“As I’ve sat down with veterans in rural areas across Georgia, one of their key concerns is lack of transportation,” Sen. Ossoff said. “That’s why I’m introducing this bipartisan bill to ensure veterans have more access to transportation services that can bring them to VA clinics and medical centers to get the care they need.”
Amanda Flener and her husband, John, a veteran wounded while serving in Iraq, were driving as long as 3 hours from Fitzgerald, Georgia (population 8900) to attend his medical appointments. In the last 2 years, Flener told the Daily Yonder she had put nearly 72,000 miles on her vehicle. Following hurricane Helene, she said, "We had been driving 30 miles just to get gas to power our generator … and we were fortunate to be able to do that.”
Telehealth appointments can help fill coverage gaps, Flener said. But even while paying for the most expensive internet plan available in her county, the signal isn't always strong enough. Telehealth care is "progress, for sure," Flener said. "So, we pay for the best Wi-Fi we can get in our area, but it isn't always reliable enough to take the video calls from the VA."
As a result, veterans and their caregivers could benefit not only from the bipartisan transportation proposal, but also from a decision announced in November. The VA is proposing to eliminate copayments for all VA telehealth services and establish a grant program to fund designated VA telehealth access points in non-VA facilities, with a focus on rural and medically underserved communities.
The program, called Accessing Telehealth through Local Area Stations (ATLAS), would provide funding to organizations — including nonprofits and private businesses — to offer veterans comfortable, private spaces equipped with high-speed internet access and the technology to remotely meet with VA clinicians. Grants would also provide designated funding to train on-site personnel to support the program.
These proposed changes would advance the VA’s and the Biden-Harris Administration’s ongoing efforts to lower costs and expand access to care for veterans. They also could make a life-changing difference for the 2.7 million rural veterans enrolled in VA health care.
According to a 2024 RAND study, just under half of military and veteran caregivers live in a county without a VA facility, and nearly half live in a primary care physician shortage area. For military/veteran caregivers in particular, the survey found, reduced access to support related to the more complicated care some patients require, greater distances to reach opportunities (eg, retail, economic, or social), and even differences in Wi-Fi/broadband internet access may create “unique needs.” The survey found that 24% of rural military/veteran caregivers did not have reliable broadband internet.
“Waiving copays for telehealth services and launching this grant program are both major steps forward in ensuring veterans can access health care where and when they need it,” said VA Secretary Denis McDonough. “VA is the best and most affordable care in America for veterans — with these steps, we can make it easier for veterans to access their earned VA health care.”
The rulemaking can be viewed in the Federal Register under public inspection, and is open for comment. The VA anticipates a notice of funding opportunity for this grant program following publication of the final rule.
Untreated Infertility Linked to Higher Risk for Systemic Autoimmune Rheumatic Disease After Childbirth
TOPLINE:
The association persists even after accounting for adverse pregnancy outcomes. Women who have experienced infertility without fertility treatment show a 25% higher risk for systemic autoimmune rheumatic disease (SARD) up to 9 years after delivery, compared with those without infertility.
METHODOLOGY:
- Population-based cohort study analyzed 568,053 singleton births among 465,078 women aged 18-50 years without pre-existing SARD in Ontario, Canada, from 2012 to 2021.
- Participants were categorized into four groups: No infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with noninvasive fertility treatment (1.4%), and infertility with invasive fertility treatment (1.4%).
- Researchers used marginal structural Cox proportional hazards models to generate hazard ratios and 95% CIs, adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes.
- Analysis included a median follow-up duration of 6.5 years (interquartile range: 4-9 years) from delivery date until SARD diagnosis, death, loss of health insurance, or study end.
TAKEAWAY:
- The incidence rate of SARD was 12.5 per 10,000 person-years in women with untreated infertility, compared with 9.3 per 10,000 person-years in women without infertility.
- Women with untreated infertility showed an elevated risk for SARD (controlled direct effect hazard ratio [HR], 1.25; 95% CI, 1.12-1.40) even after accounting for adverse pregnancy outcomes.
- Neither noninvasive fertility treatment (total effect HR, 1.06; 95% CI, 0.79-1.42) nor invasive fertility treatment (total effect HR, 0.97; 95% CI, 0.69-1.36) were associated with increased SARD risk.
- The association between untreated infertility and SARD persisted in analyses restricted to women aged < 38 years and in those without endometriosis or other autoimmune diseases.
IN PRACTICE:
“Future research efforts should seek to corroborate this association by infertility cause, with a focus on possible mechanisms related to ovulatory, ovarian, and sexual dysfunction. Greater health provider awareness of SARD symptoms and related gynecological issues that may present in women with infertility could facilitate earlier detection and treatment of SARD during the reproductive years,” wrote the authors of the study.
SOURCE:
The study was led by Natalie V. Scime of the Department of Health and Society, University of Toronto Scarborough in Ontario, Canada. It was published online in Human Reproduction.
LIMITATIONS:
Exposure and outcome misclassification was possible due to the use of published algorithms in health administrative data with unknown or imperfect sensitivity and specificity. The researchers noted that individual-level social and lifestyle factors and underlying causes of infertility were not available, and thus, were not included in the analysis.
DISCLOSURES:
This research received funding through a Banting Postdoctoral Fellowship to Scime and Canada Research Chair to Hilary K. Brown (2019-00158), with support from ICES, funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. One coauthor disclosed consulting for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, Mallinckrodt Canada, and GlaxoSmithKline. All other authors reported no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
The association persists even after accounting for adverse pregnancy outcomes. Women who have experienced infertility without fertility treatment show a 25% higher risk for systemic autoimmune rheumatic disease (SARD) up to 9 years after delivery, compared with those without infertility.
METHODOLOGY:
- Population-based cohort study analyzed 568,053 singleton births among 465,078 women aged 18-50 years without pre-existing SARD in Ontario, Canada, from 2012 to 2021.
- Participants were categorized into four groups: No infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with noninvasive fertility treatment (1.4%), and infertility with invasive fertility treatment (1.4%).
- Researchers used marginal structural Cox proportional hazards models to generate hazard ratios and 95% CIs, adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes.
- Analysis included a median follow-up duration of 6.5 years (interquartile range: 4-9 years) from delivery date until SARD diagnosis, death, loss of health insurance, or study end.
TAKEAWAY:
- The incidence rate of SARD was 12.5 per 10,000 person-years in women with untreated infertility, compared with 9.3 per 10,000 person-years in women without infertility.
- Women with untreated infertility showed an elevated risk for SARD (controlled direct effect hazard ratio [HR], 1.25; 95% CI, 1.12-1.40) even after accounting for adverse pregnancy outcomes.
- Neither noninvasive fertility treatment (total effect HR, 1.06; 95% CI, 0.79-1.42) nor invasive fertility treatment (total effect HR, 0.97; 95% CI, 0.69-1.36) were associated with increased SARD risk.
- The association between untreated infertility and SARD persisted in analyses restricted to women aged < 38 years and in those without endometriosis or other autoimmune diseases.
IN PRACTICE:
“Future research efforts should seek to corroborate this association by infertility cause, with a focus on possible mechanisms related to ovulatory, ovarian, and sexual dysfunction. Greater health provider awareness of SARD symptoms and related gynecological issues that may present in women with infertility could facilitate earlier detection and treatment of SARD during the reproductive years,” wrote the authors of the study.
SOURCE:
The study was led by Natalie V. Scime of the Department of Health and Society, University of Toronto Scarborough in Ontario, Canada. It was published online in Human Reproduction.
LIMITATIONS:
Exposure and outcome misclassification was possible due to the use of published algorithms in health administrative data with unknown or imperfect sensitivity and specificity. The researchers noted that individual-level social and lifestyle factors and underlying causes of infertility were not available, and thus, were not included in the analysis.
DISCLOSURES:
This research received funding through a Banting Postdoctoral Fellowship to Scime and Canada Research Chair to Hilary K. Brown (2019-00158), with support from ICES, funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. One coauthor disclosed consulting for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, Mallinckrodt Canada, and GlaxoSmithKline. All other authors reported no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
The association persists even after accounting for adverse pregnancy outcomes. Women who have experienced infertility without fertility treatment show a 25% higher risk for systemic autoimmune rheumatic disease (SARD) up to 9 years after delivery, compared with those without infertility.
METHODOLOGY:
- Population-based cohort study analyzed 568,053 singleton births among 465,078 women aged 18-50 years without pre-existing SARD in Ontario, Canada, from 2012 to 2021.
- Participants were categorized into four groups: No infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with noninvasive fertility treatment (1.4%), and infertility with invasive fertility treatment (1.4%).
- Researchers used marginal structural Cox proportional hazards models to generate hazard ratios and 95% CIs, adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes.
- Analysis included a median follow-up duration of 6.5 years (interquartile range: 4-9 years) from delivery date until SARD diagnosis, death, loss of health insurance, or study end.
TAKEAWAY:
- The incidence rate of SARD was 12.5 per 10,000 person-years in women with untreated infertility, compared with 9.3 per 10,000 person-years in women without infertility.
- Women with untreated infertility showed an elevated risk for SARD (controlled direct effect hazard ratio [HR], 1.25; 95% CI, 1.12-1.40) even after accounting for adverse pregnancy outcomes.
- Neither noninvasive fertility treatment (total effect HR, 1.06; 95% CI, 0.79-1.42) nor invasive fertility treatment (total effect HR, 0.97; 95% CI, 0.69-1.36) were associated with increased SARD risk.
- The association between untreated infertility and SARD persisted in analyses restricted to women aged < 38 years and in those without endometriosis or other autoimmune diseases.
IN PRACTICE:
“Future research efforts should seek to corroborate this association by infertility cause, with a focus on possible mechanisms related to ovulatory, ovarian, and sexual dysfunction. Greater health provider awareness of SARD symptoms and related gynecological issues that may present in women with infertility could facilitate earlier detection and treatment of SARD during the reproductive years,” wrote the authors of the study.
SOURCE:
The study was led by Natalie V. Scime of the Department of Health and Society, University of Toronto Scarborough in Ontario, Canada. It was published online in Human Reproduction.
LIMITATIONS:
Exposure and outcome misclassification was possible due to the use of published algorithms in health administrative data with unknown or imperfect sensitivity and specificity. The researchers noted that individual-level social and lifestyle factors and underlying causes of infertility were not available, and thus, were not included in the analysis.
DISCLOSURES:
This research received funding through a Banting Postdoctoral Fellowship to Scime and Canada Research Chair to Hilary K. Brown (2019-00158), with support from ICES, funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. One coauthor disclosed consulting for Celltrion, Werfen, Organon, MitogenDx, AstraZeneca, Mallinckrodt Canada, and GlaxoSmithKline. All other authors reported no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.