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Nicotine patch may be an effective precision therapy for select epilepsies
NEW ORLEANS – according to research presented at the annual meeting of the American Epilepsy Society. Of four epilepsy patients at one center who received nicotine-patch treatment, three had a good clinical response, one of whom became seizure free.
“We confirm that, in select patients, treatment with a nicotine patch ... can be an effective precision therapy for epilepsy. We propose consideration of nicotine-patch treatment in refractory patients with known cholinergic nicotine receptor subunit variants, especially those with a clinical history consistent with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE),” said Jordana Fox, DO, and Alison Dolce, MD, both with the University of Texas Southwestern Medical Center in Dallas.
Gene variants in CHRAn4,CHRNA2, and CHRNB2 can cause ADNFLE. Preclinical and n-of-1 studies have suggested that nicotine may be a precision treatment for ADNFLE.
Dr. Fox and Dr. Dolce reviewed next-generation sequencing epilepsy panels from patients seen at Children’s Medical Center, Dallas, during 2011-2015 to identify patients with nAChR gene variants (CHNRA4, CHRNA2, CHRNB2, and CHRNA7). They reviewed patients’ medical and laboratory records, including genetic variant details and treatment history, and focused on patients who underwent a trial of nicotine-patch treatment.
Of the 21 patients who had nAChR gene variants, 4 tried treatment with a nicotine patch, either 7 mg or 14 mg. The patients who received nicotine-patch treatment had genetic variants in CHRNA4, CHRNB2, and CHRNA2. Three of the patients who tried nicotine-patch treatment had a greater than 50% reduction in seizures, whereas one had no treatment response.
“One patient became seizure free and is now treated with the nicotine patch as monotherapy,” Dr. Fox said.
The patient with complete resolution of seizures had a heterozygous disease–causing mutation in CHRNB2. This patient had nocturnal focal seizures, normal neuroimaging, and had been receiving treatment with oxcarbazepine and zonisamide.
The review identified four patients with nAChR gene variants and the ADNFLE phenotype who have not been treated with nicotine. Further phenotype-genotype characterizations and preclinical studies will help neurologists understand the mechanisms of these complex gene variants.
The researchers received no funding for the study and had no relevant financial disclosures.
SOURCE: Fox J et al. AES 2018, Abstract 1.230.
NEW ORLEANS – according to research presented at the annual meeting of the American Epilepsy Society. Of four epilepsy patients at one center who received nicotine-patch treatment, three had a good clinical response, one of whom became seizure free.
“We confirm that, in select patients, treatment with a nicotine patch ... can be an effective precision therapy for epilepsy. We propose consideration of nicotine-patch treatment in refractory patients with known cholinergic nicotine receptor subunit variants, especially those with a clinical history consistent with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE),” said Jordana Fox, DO, and Alison Dolce, MD, both with the University of Texas Southwestern Medical Center in Dallas.
Gene variants in CHRAn4,CHRNA2, and CHRNB2 can cause ADNFLE. Preclinical and n-of-1 studies have suggested that nicotine may be a precision treatment for ADNFLE.
Dr. Fox and Dr. Dolce reviewed next-generation sequencing epilepsy panels from patients seen at Children’s Medical Center, Dallas, during 2011-2015 to identify patients with nAChR gene variants (CHNRA4, CHRNA2, CHRNB2, and CHRNA7). They reviewed patients’ medical and laboratory records, including genetic variant details and treatment history, and focused on patients who underwent a trial of nicotine-patch treatment.
Of the 21 patients who had nAChR gene variants, 4 tried treatment with a nicotine patch, either 7 mg or 14 mg. The patients who received nicotine-patch treatment had genetic variants in CHRNA4, CHRNB2, and CHRNA2. Three of the patients who tried nicotine-patch treatment had a greater than 50% reduction in seizures, whereas one had no treatment response.
“One patient became seizure free and is now treated with the nicotine patch as monotherapy,” Dr. Fox said.
The patient with complete resolution of seizures had a heterozygous disease–causing mutation in CHRNB2. This patient had nocturnal focal seizures, normal neuroimaging, and had been receiving treatment with oxcarbazepine and zonisamide.
The review identified four patients with nAChR gene variants and the ADNFLE phenotype who have not been treated with nicotine. Further phenotype-genotype characterizations and preclinical studies will help neurologists understand the mechanisms of these complex gene variants.
The researchers received no funding for the study and had no relevant financial disclosures.
SOURCE: Fox J et al. AES 2018, Abstract 1.230.
NEW ORLEANS – according to research presented at the annual meeting of the American Epilepsy Society. Of four epilepsy patients at one center who received nicotine-patch treatment, three had a good clinical response, one of whom became seizure free.
“We confirm that, in select patients, treatment with a nicotine patch ... can be an effective precision therapy for epilepsy. We propose consideration of nicotine-patch treatment in refractory patients with known cholinergic nicotine receptor subunit variants, especially those with a clinical history consistent with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE),” said Jordana Fox, DO, and Alison Dolce, MD, both with the University of Texas Southwestern Medical Center in Dallas.
Gene variants in CHRAn4,CHRNA2, and CHRNB2 can cause ADNFLE. Preclinical and n-of-1 studies have suggested that nicotine may be a precision treatment for ADNFLE.
Dr. Fox and Dr. Dolce reviewed next-generation sequencing epilepsy panels from patients seen at Children’s Medical Center, Dallas, during 2011-2015 to identify patients with nAChR gene variants (CHNRA4, CHRNA2, CHRNB2, and CHRNA7). They reviewed patients’ medical and laboratory records, including genetic variant details and treatment history, and focused on patients who underwent a trial of nicotine-patch treatment.
Of the 21 patients who had nAChR gene variants, 4 tried treatment with a nicotine patch, either 7 mg or 14 mg. The patients who received nicotine-patch treatment had genetic variants in CHRNA4, CHRNB2, and CHRNA2. Three of the patients who tried nicotine-patch treatment had a greater than 50% reduction in seizures, whereas one had no treatment response.
“One patient became seizure free and is now treated with the nicotine patch as monotherapy,” Dr. Fox said.
The patient with complete resolution of seizures had a heterozygous disease–causing mutation in CHRNB2. This patient had nocturnal focal seizures, normal neuroimaging, and had been receiving treatment with oxcarbazepine and zonisamide.
The review identified four patients with nAChR gene variants and the ADNFLE phenotype who have not been treated with nicotine. Further phenotype-genotype characterizations and preclinical studies will help neurologists understand the mechanisms of these complex gene variants.
The researchers received no funding for the study and had no relevant financial disclosures.
SOURCE: Fox J et al. AES 2018, Abstract 1.230.
REPORTING FROM AES 2018
Key clinical point: In select patients with epilepsy, nicotine may be an effective precision therapy.
Major finding: Of four patients who received nicotine-patch treatment at one center, three had a good clinical response, one of whom became seizure free.
Study details: Single-center chart review of 21 patients with gene variants in subunits of the nicotinic acetylcholine receptor.
Disclosures: The researchers received no funding for the study and had no relevant financial disclosures.
Source: Fox J et al. AES 2018, Abstract 1.230.
Rapid test could solve Africa’s sickle cell screening problem
SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.
The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.
Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.
“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.
Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.
Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.
“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.
Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.
In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.
The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.
Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.
Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).
Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.
Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.
On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.
This article was updated on 3/14/2019.
SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.
SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.
The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.
Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.
“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.
Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.
Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.
“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.
Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.
In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.
The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.
Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.
Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).
Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.
Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.
On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.
This article was updated on 3/14/2019.
SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.
SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.
The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.
Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.
“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.
Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.
Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.
“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.
Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.
In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.
The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.
Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.
Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).
Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.
Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.
On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.
This article was updated on 3/14/2019.
SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The assay had an overall accuracy of 99.8% in correctly identifying phenotypes as initially determined by hemoglobin electrophoresis.
Study details: A diagnostic accuracy study including 1,000 children aged 5 years and younger were prospectively recruited from hospitals and outpatient clinics in Uganda.
Disclosures: Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study and makes the test.
Source: Serrao E et al. ASH 2018, Abstract LBA-3.
Common AEDs confer modestly increased risk of major congenital malformations
NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic (MONEAD) study is quite reassuring, Kimford J. Meador, MD, said at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.
At baseline, all the women had a mean age of about 30 years. Most (75%) were on monotherapy, 20% were on polytherapy, and the rest were not taking an AED. About 60% had focal epilepsy, 31% had generalized epilepsy, and the remainder had an unclassified seizure disorder. Three subjects had multiple seizure types. The most commonly used AEDs were lamotrigine and levetiracetam (both about 30%); 4% were taking zonisamide, 4% carbamazepine, and 4% oxcarbazepine. Topiramate was being used for 2% of the pregnant woman and 5% of the nonpregnant woman. The combination of lamotrigine and levetiracetam was used for 9.0% of pregnant and 5.5% of nonpregnant women, and other polytherapies in 12.0% of the pregnant and 14.0% of the nonpregnant woman. About 4% of the pregnant and 1% of the nonpregnant women were not taking any AED.
There were 10 (2.8%) spontaneous miscarriages among the pregnant women with epilepsy and none among the healthy pregnant women. Spontaneous miscarriages weren’t associated with acute seizures, and there were no major congenital malformations reported among them. There were also two elective abortions among the pregnant women with epilepsy.
There were 18 major congenital malformations among the pregnant woman with epilepsy (5%). A total of 14 were among pregnancies exposed to monotherapy, 3 were in polytherapy-exposed pregnancies, and 1 was in the group not taking any AEDs.
The malformations were:
- Carbamazepine (one case) – hydronephrosis.
- Gabapentin (one case) – inguinal hernia.
- Lamotrigine (five cases) – aortic coarctation, cryptorchidism, hydronephrosis, pectus excavatum, and morning glory syndrome (a funnel-shaped optic nerve disc associated with impaired visual acuity).
- Levetiracetam (five cases) – atrial septal defect, buried penis syndrome, cryptorchidism, hypoplastic aortic valve, ventricular septal defect.
- Topiramate (one case) – ventricular septal defect.
- Zonisamide (one case) – inguinal hernia, absent pinna.
- Lamotrigine plus clonazepam (one case) – cardiomyopathy.
- Lamotrigine plus levetiracetam (one case) – microcephaly, myelomeningocele, Chiari II malformation.
- Levetiracetam plus phenobarbital (one case) – bilateral inguinal hernia.
MONEAD is funded by the National Institutes of Health; Dr. Meador reported no financial disclosures.
SOURCE: Meador KJ et al. AES 2018, Abstract 3.231.
NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic (MONEAD) study is quite reassuring, Kimford J. Meador, MD, said at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.
At baseline, all the women had a mean age of about 30 years. Most (75%) were on monotherapy, 20% were on polytherapy, and the rest were not taking an AED. About 60% had focal epilepsy, 31% had generalized epilepsy, and the remainder had an unclassified seizure disorder. Three subjects had multiple seizure types. The most commonly used AEDs were lamotrigine and levetiracetam (both about 30%); 4% were taking zonisamide, 4% carbamazepine, and 4% oxcarbazepine. Topiramate was being used for 2% of the pregnant woman and 5% of the nonpregnant woman. The combination of lamotrigine and levetiracetam was used for 9.0% of pregnant and 5.5% of nonpregnant women, and other polytherapies in 12.0% of the pregnant and 14.0% of the nonpregnant woman. About 4% of the pregnant and 1% of the nonpregnant women were not taking any AED.
There were 10 (2.8%) spontaneous miscarriages among the pregnant women with epilepsy and none among the healthy pregnant women. Spontaneous miscarriages weren’t associated with acute seizures, and there were no major congenital malformations reported among them. There were also two elective abortions among the pregnant women with epilepsy.
There were 18 major congenital malformations among the pregnant woman with epilepsy (5%). A total of 14 were among pregnancies exposed to monotherapy, 3 were in polytherapy-exposed pregnancies, and 1 was in the group not taking any AEDs.
The malformations were:
- Carbamazepine (one case) – hydronephrosis.
- Gabapentin (one case) – inguinal hernia.
- Lamotrigine (five cases) – aortic coarctation, cryptorchidism, hydronephrosis, pectus excavatum, and morning glory syndrome (a funnel-shaped optic nerve disc associated with impaired visual acuity).
- Levetiracetam (five cases) – atrial septal defect, buried penis syndrome, cryptorchidism, hypoplastic aortic valve, ventricular septal defect.
- Topiramate (one case) – ventricular septal defect.
- Zonisamide (one case) – inguinal hernia, absent pinna.
- Lamotrigine plus clonazepam (one case) – cardiomyopathy.
- Lamotrigine plus levetiracetam (one case) – microcephaly, myelomeningocele, Chiari II malformation.
- Levetiracetam plus phenobarbital (one case) – bilateral inguinal hernia.
MONEAD is funded by the National Institutes of Health; Dr. Meador reported no financial disclosures.
SOURCE: Meador KJ et al. AES 2018, Abstract 3.231.
NEW ORLEANS – The most commonly used antiepileptic drugs modestly increased the risk of major congenital malformations among prenatally exposed infants in the MONEAD study.
Malformations occurred among 5% of pregnancies exposed to the medications – higher than the 2% background rate – but this was still much lower than the 9%-10% rate associated with valproate.
Overall, however, the message of the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic (MONEAD) study is quite reassuring, Kimford J. Meador, MD, said at the annual meeting of the American Epilepsy Society. MONEAD is an ongoing, prospective study to determine both maternal outcomes and long-term childhood neurodevelopmental outcomes associated with the use of antiepileptic drugs (AEDs) during pregnancy.
“The rate of malformations was higher than I thought it would be, and higher than the 2% background rate, but it’s still a modest increase and most babies are born completely normal,” Dr. Meador, professor of neurology and neurosciences at Stanford (Calif.) University, said in an interview. “I think the news here is good, and it’s especially reassuring when you put it in the context that, 60 years ago, there were laws that women with epilepsy couldn’t get married, and some states even had laws to sterilize women. I think that’s absurd when most infants born to these women are without malformations and the risk of miscarriage is very low.”
Another positive finding, he said, is that valproate use among pregnant women is now practically nonexistent. Only 1 of 351 pregnant women with epilepsy and just 2 of a comparator group of 109 nonpregnant women with epilepsy were taking it. That’s great news, said Dr. Meador, who also initiated the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study in the early 2000s. NEAD determined the drug’s serious teratogenic potential.
In addition to the cohorts of pregnant and nonpregnant women with epilepsy, 105 healthy pregnant women enrolled in the MONEAD study. Women will be monitored during pregnancy and postpartum to measure maternal outcomes and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes.
The study has six primary outcomes, three for the women and three for their children.
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors.
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors.
- Determine if women with epilepsy have an increased risk for depression during pregnancy and the postpartum period and characterize risk factors.
- Determine the long-term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes.
- Determine if small-for-gestational age and other adverse neonatal outcomes are increased.
- Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.
Rates of miscarriage and neonatal malformations were not primary study outcomes, but the descriptive data were collected and are of high interest, Dr. Meador said.
At baseline, all the women had a mean age of about 30 years. Most (75%) were on monotherapy, 20% were on polytherapy, and the rest were not taking an AED. About 60% had focal epilepsy, 31% had generalized epilepsy, and the remainder had an unclassified seizure disorder. Three subjects had multiple seizure types. The most commonly used AEDs were lamotrigine and levetiracetam (both about 30%); 4% were taking zonisamide, 4% carbamazepine, and 4% oxcarbazepine. Topiramate was being used for 2% of the pregnant woman and 5% of the nonpregnant woman. The combination of lamotrigine and levetiracetam was used for 9.0% of pregnant and 5.5% of nonpregnant women, and other polytherapies in 12.0% of the pregnant and 14.0% of the nonpregnant woman. About 4% of the pregnant and 1% of the nonpregnant women were not taking any AED.
There were 10 (2.8%) spontaneous miscarriages among the pregnant women with epilepsy and none among the healthy pregnant women. Spontaneous miscarriages weren’t associated with acute seizures, and there were no major congenital malformations reported among them. There were also two elective abortions among the pregnant women with epilepsy.
There were 18 major congenital malformations among the pregnant woman with epilepsy (5%). A total of 14 were among pregnancies exposed to monotherapy, 3 were in polytherapy-exposed pregnancies, and 1 was in the group not taking any AEDs.
The malformations were:
- Carbamazepine (one case) – hydronephrosis.
- Gabapentin (one case) – inguinal hernia.
- Lamotrigine (five cases) – aortic coarctation, cryptorchidism, hydronephrosis, pectus excavatum, and morning glory syndrome (a funnel-shaped optic nerve disc associated with impaired visual acuity).
- Levetiracetam (five cases) – atrial septal defect, buried penis syndrome, cryptorchidism, hypoplastic aortic valve, ventricular septal defect.
- Topiramate (one case) – ventricular septal defect.
- Zonisamide (one case) – inguinal hernia, absent pinna.
- Lamotrigine plus clonazepam (one case) – cardiomyopathy.
- Lamotrigine plus levetiracetam (one case) – microcephaly, myelomeningocele, Chiari II malformation.
- Levetiracetam plus phenobarbital (one case) – bilateral inguinal hernia.
MONEAD is funded by the National Institutes of Health; Dr. Meador reported no financial disclosures.
SOURCE: Meador KJ et al. AES 2018, Abstract 3.231.
REPORTING FROM AES 2018
Key clinical point:
Major finding: The malformation rate was 5% in exposed pregnancies.
Study details: The MONEAD study comprised 351 pregnant women with epilepsy, 109 nonpregnant women with epilepsy, and 105 healthy pregnant women.
Disclosures: The National Institutes of Health funded the study; Dr. Meador reported no financial disclosures.
Source: Meador KJ et al. AES 2018, Abstract 3.231.
Tender joint count may confound assessment of RA inflammation
In RA, patients with predominantly tender joint counts were found to have lower levels of inflammation defined by ultrasound than those with predominantly swollen joints, according to an observational study that has implications for management decisions.
When patients do not achieve a remission defined by a composite disease activity score (CDAS) that includes tender joint counts, it suggests that inflammation persists, but this may be a “misinterpretation,” according to a report in Arthritis Care & Research by Hilde B. Hammer, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital, Oslo, and her associates.
In this observational study, 209 RA patients were evaluated at baseline and again at months 1, 2, 3, 6, and 12. The researchers compared 84 patients with predominantly tender joints, defined as tender-swollen joint count difference (TSJD) score of greater than zero, against 125 patients with predominantly swollen joints, defined as TSJD of zero or less.
Scores on specific CDAS measures, such as the Disease Activity Score based on 28 joints, the Clinical Disease Activity Index, and the Simplified Disease Activity Index, were significantly higher (P less than .001) at all visits in patients with predominantly tender joints, compared with those with predominantly swollen joints. Although laboratory markers, such as C-reactive protein and rheumatoid factor, were similar between groups, synovitis as scored with ultrasound assessment was significantly lower (P less than .001) among patients with predominantly tender joints than in those with predominantly swollen joints.
This disparity is important, according to the authors, who suggested that failure to reach a CDAS-defined remission solely on the basis of tender joints might complicate clinical assessment.
“Taking the high impact of CDAS levels in the treat-to-target management of RA into account, our results suggest a careful interpretation of CDAS levels in patients who have predominantly tender joints,” the authors reported.
Based on the evidence from this study, which found tender joints to be a positive predictor of CDAS and patient-reported outcomes but a negative predictor of ultrasound scoring of inflammation, “these results indicate that tender joints do not reflect the same pathology as found with ultrasound,” they wrote.
The research was supported by AbbVie, Pfizer, and Roche in the form of study grants awarded to the department of rheumatology at Diakonhjemmet Hospital via Dr. Hammer and two other authors. Dr. Hammer and the two other authors also reported financial relationships with those companies and others.
SOURCE: Hammer HB et al. Arthritis Care Res. 2018 Nov 26. doi: 10.1002/acr.23815.
In RA, patients with predominantly tender joint counts were found to have lower levels of inflammation defined by ultrasound than those with predominantly swollen joints, according to an observational study that has implications for management decisions.
When patients do not achieve a remission defined by a composite disease activity score (CDAS) that includes tender joint counts, it suggests that inflammation persists, but this may be a “misinterpretation,” according to a report in Arthritis Care & Research by Hilde B. Hammer, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital, Oslo, and her associates.
In this observational study, 209 RA patients were evaluated at baseline and again at months 1, 2, 3, 6, and 12. The researchers compared 84 patients with predominantly tender joints, defined as tender-swollen joint count difference (TSJD) score of greater than zero, against 125 patients with predominantly swollen joints, defined as TSJD of zero or less.
Scores on specific CDAS measures, such as the Disease Activity Score based on 28 joints, the Clinical Disease Activity Index, and the Simplified Disease Activity Index, were significantly higher (P less than .001) at all visits in patients with predominantly tender joints, compared with those with predominantly swollen joints. Although laboratory markers, such as C-reactive protein and rheumatoid factor, were similar between groups, synovitis as scored with ultrasound assessment was significantly lower (P less than .001) among patients with predominantly tender joints than in those with predominantly swollen joints.
This disparity is important, according to the authors, who suggested that failure to reach a CDAS-defined remission solely on the basis of tender joints might complicate clinical assessment.
“Taking the high impact of CDAS levels in the treat-to-target management of RA into account, our results suggest a careful interpretation of CDAS levels in patients who have predominantly tender joints,” the authors reported.
Based on the evidence from this study, which found tender joints to be a positive predictor of CDAS and patient-reported outcomes but a negative predictor of ultrasound scoring of inflammation, “these results indicate that tender joints do not reflect the same pathology as found with ultrasound,” they wrote.
The research was supported by AbbVie, Pfizer, and Roche in the form of study grants awarded to the department of rheumatology at Diakonhjemmet Hospital via Dr. Hammer and two other authors. Dr. Hammer and the two other authors also reported financial relationships with those companies and others.
SOURCE: Hammer HB et al. Arthritis Care Res. 2018 Nov 26. doi: 10.1002/acr.23815.
In RA, patients with predominantly tender joint counts were found to have lower levels of inflammation defined by ultrasound than those with predominantly swollen joints, according to an observational study that has implications for management decisions.
When patients do not achieve a remission defined by a composite disease activity score (CDAS) that includes tender joint counts, it suggests that inflammation persists, but this may be a “misinterpretation,” according to a report in Arthritis Care & Research by Hilde B. Hammer, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital, Oslo, and her associates.
In this observational study, 209 RA patients were evaluated at baseline and again at months 1, 2, 3, 6, and 12. The researchers compared 84 patients with predominantly tender joints, defined as tender-swollen joint count difference (TSJD) score of greater than zero, against 125 patients with predominantly swollen joints, defined as TSJD of zero or less.
Scores on specific CDAS measures, such as the Disease Activity Score based on 28 joints, the Clinical Disease Activity Index, and the Simplified Disease Activity Index, were significantly higher (P less than .001) at all visits in patients with predominantly tender joints, compared with those with predominantly swollen joints. Although laboratory markers, such as C-reactive protein and rheumatoid factor, were similar between groups, synovitis as scored with ultrasound assessment was significantly lower (P less than .001) among patients with predominantly tender joints than in those with predominantly swollen joints.
This disparity is important, according to the authors, who suggested that failure to reach a CDAS-defined remission solely on the basis of tender joints might complicate clinical assessment.
“Taking the high impact of CDAS levels in the treat-to-target management of RA into account, our results suggest a careful interpretation of CDAS levels in patients who have predominantly tender joints,” the authors reported.
Based on the evidence from this study, which found tender joints to be a positive predictor of CDAS and patient-reported outcomes but a negative predictor of ultrasound scoring of inflammation, “these results indicate that tender joints do not reflect the same pathology as found with ultrasound,” they wrote.
The research was supported by AbbVie, Pfizer, and Roche in the form of study grants awarded to the department of rheumatology at Diakonhjemmet Hospital via Dr. Hammer and two other authors. Dr. Hammer and the two other authors also reported financial relationships with those companies and others.
SOURCE: Hammer HB et al. Arthritis Care Res. 2018 Nov 26. doi: 10.1002/acr.23815.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: Baseline tender joint count correlates with patient-reported outcomes (P less than .001) but not with ultrasound-assessed inflammation.
Study details: An observational study of 209 RA patients.
Disclosures: The research was supported by AbbVie, Pfizer, and Roche in the form of study grants awarded to the department of rheumatology at Diakonhjemmet Hospital via Dr. Hammer and two other authors. Dr. Hammer and the two other authors also reported financial relationships with those companies and others.
Source: Hammer HB et al. Arthritis Care Res. 2018 Nov 26. doi: 10.1002/acr.23815.
Breastfeeding with MS: Good for mom, too
BERLIN – In the changing multiple sclerosis landscape, more women are having babies, and more are asking questions. With these women, what’s the best way to address the complicated interplay among pregnancy, relapse risk, breastfeeding, and medication resumption? A starting point is to recognize that “women with MS are very different today than they were 25 years ago,” said Annette Langer-Gould, MD, PhD. Not only have diagnostic criteria changed but also highly effective treatments now exist that were not available when the first pregnancy cohorts were studied, she pointed out, speaking at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.
The existing literature, said Dr. Langer-Gould, has addressed one controversy: “Most women with MS can have normal pregnancies – and breastfeed – without incurring harm,” though it’s true that severe rebound relapses are possible if natalizumab (Tysabri) or fingolimod (Gilenya) are stopped before pregnancy. In any case, new small-molecule MS medications need to be stopped during pregnancy and breastfeeding, she pointed out. “We didn’t have to worry about that too much when we only had injectables and monoclonal antibodies because they were larger and didn’t cross the placenta.”
Since the 1980s, the conversation about pregnancy and MS has moved from asking “Is pregnancy bad for women with MS?” to the current MS landscape, in which sicker women are able to become pregnant, Dr. Langer-Gould said, adding that how women with MS fare through pregnancy and in the postpartum period is changing over time as well. She and her colleagues’ experience with pregnancy in a cohort of women with MS in the Kaiser Permanente care system, where she is a clinical neurologist and regional research lead, revealed a relapse rate of 8.4%. “So it was pretty rare for a woman to have a relapse during pregnancy,” Dr. Langer-Gould said.
Most women with MS who become pregnant, whether their care is received in a referral center or is community based, are now doing so while on a disease-modifying therapy (DMT), Dr. Langer-Gould said. On these highly effective treatments, “women who were too sick to get pregnant are now well controlled and having babies.”
As more women with MS become pregnant, more conversations about breastfeeding will inevitably crop up, she said. And the discussion about breastfeeding has now begun to acknowledge the “strong benefits to mom and the baby of not just breastfeeding, but longer breastfeeding,” as well.
“Because of this baby-friendly push in a lot of hospitals in the United States, where they’re trying to encourage all women to breastfeed,” a full 87% of women breastfed their infants at least some of the time, and over a third of women (35%) breastfed exclusively for at least 2 months, Dr. Langer-Gould said.
“There’s no one clear explanation of why the women seem to be healthier and doing better through pregnancy as a group, but it’s probably a combination of having milder disease, breastfeeding more, and they’ve got better controlled disease before pregnancy,” she said.
At least eight studies to date have examined the relationship between postpartum MS relapses and breastfeeding, Dr. Langer-Gould said.
“The thing to take away ... is that, even though we’ve studied this many, many times, no one can show that it’s harmful,” she said. For mothers who want to breastfeed, “you can support them in the breastfeeding choice, because they are not going to have more severe disease because of that.”
Whether breastfeeding is exclusive or not has not always been tracked in studies of childbearing women with MS, but when it was captured in the data, exclusive breastfeeding has exerted a protective effect, with about a 50% reduction in risk for postpartum relapse seen in one study (JAMA Neurol. 2015 Oct;72[10]:1132-8).
There is a hormonal rationale for exclusive breastfeeding exerting a protective effect on MS: With exclusive breastfeeding comes more frequent, intense suckling, with more profound elevations in prolactin, and larger drops in follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. All these hormonal changes work together to produce more prolonged amenorrhea and anovulation, Dr. Langer-Gould said, with potentially beneficial immunologic effects.
When other, more general maternal and infant health benefits of breastfeeding also are taken into account, there’s strong evidence for the benefits of breastfeeding for women with MS whose medication profile allows them to breastfeed, she said.
However, the “treatment” effect of exclusive breastfeeding is only effective until the infant starts taking regular supplemental feedings, including the introduction of table food at around 6 months of age. “Once regular supplemental feedings are introduced, relapses return,” Dr. Langer-Gould said.
There is some suggestion that, in women without MS, prolonged breastfeeding may be associated with reduced risk of MS. In the MS Sunshine study, breastfeeding for 15 months or longer decreased the risk of later MS by 23%-53% (Nutrients. 2018 Feb 27;10[3]:268). The investigators, led by Dr. Langer-Gould, summed the total months of breastfeeding across all children, so that the 15-month threshold could be reached by breastfeeding one child for 15 months, or three children for 5 months each. “It’s a single study; I wouldn’t make too much out of it,” Dr. Langer-Gould said.
Open questions still remain, she said: “So far, no one has been able to demonstrate a clear beneficial effect in reducing the risk of postpartum relapse if they resume their DMT early in the postpartum period.” Dr. Langer-Gould noted that the literature in this area is hampered by heterogeneity and by the fact that newer, more highly active DMTs have not been well studied.
Also, the link between postpartum relapses and long-term prognosis is not completely delineated. Indirect evidence, she said, points to a postpartum relapse as being “overall, a low-impact event.”
Dr. Langer-Gould reported that she has been the site principal investigator for clinical trials sponsored by Roche and Biogen.
SOURCE: Langer-Gould A. ECTRIMS 2018, Abstract 5.
BERLIN – In the changing multiple sclerosis landscape, more women are having babies, and more are asking questions. With these women, what’s the best way to address the complicated interplay among pregnancy, relapse risk, breastfeeding, and medication resumption? A starting point is to recognize that “women with MS are very different today than they were 25 years ago,” said Annette Langer-Gould, MD, PhD. Not only have diagnostic criteria changed but also highly effective treatments now exist that were not available when the first pregnancy cohorts were studied, she pointed out, speaking at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.
The existing literature, said Dr. Langer-Gould, has addressed one controversy: “Most women with MS can have normal pregnancies – and breastfeed – without incurring harm,” though it’s true that severe rebound relapses are possible if natalizumab (Tysabri) or fingolimod (Gilenya) are stopped before pregnancy. In any case, new small-molecule MS medications need to be stopped during pregnancy and breastfeeding, she pointed out. “We didn’t have to worry about that too much when we only had injectables and monoclonal antibodies because they were larger and didn’t cross the placenta.”
Since the 1980s, the conversation about pregnancy and MS has moved from asking “Is pregnancy bad for women with MS?” to the current MS landscape, in which sicker women are able to become pregnant, Dr. Langer-Gould said, adding that how women with MS fare through pregnancy and in the postpartum period is changing over time as well. She and her colleagues’ experience with pregnancy in a cohort of women with MS in the Kaiser Permanente care system, where she is a clinical neurologist and regional research lead, revealed a relapse rate of 8.4%. “So it was pretty rare for a woman to have a relapse during pregnancy,” Dr. Langer-Gould said.
Most women with MS who become pregnant, whether their care is received in a referral center or is community based, are now doing so while on a disease-modifying therapy (DMT), Dr. Langer-Gould said. On these highly effective treatments, “women who were too sick to get pregnant are now well controlled and having babies.”
As more women with MS become pregnant, more conversations about breastfeeding will inevitably crop up, she said. And the discussion about breastfeeding has now begun to acknowledge the “strong benefits to mom and the baby of not just breastfeeding, but longer breastfeeding,” as well.
“Because of this baby-friendly push in a lot of hospitals in the United States, where they’re trying to encourage all women to breastfeed,” a full 87% of women breastfed their infants at least some of the time, and over a third of women (35%) breastfed exclusively for at least 2 months, Dr. Langer-Gould said.
“There’s no one clear explanation of why the women seem to be healthier and doing better through pregnancy as a group, but it’s probably a combination of having milder disease, breastfeeding more, and they’ve got better controlled disease before pregnancy,” she said.
At least eight studies to date have examined the relationship between postpartum MS relapses and breastfeeding, Dr. Langer-Gould said.
“The thing to take away ... is that, even though we’ve studied this many, many times, no one can show that it’s harmful,” she said. For mothers who want to breastfeed, “you can support them in the breastfeeding choice, because they are not going to have more severe disease because of that.”
Whether breastfeeding is exclusive or not has not always been tracked in studies of childbearing women with MS, but when it was captured in the data, exclusive breastfeeding has exerted a protective effect, with about a 50% reduction in risk for postpartum relapse seen in one study (JAMA Neurol. 2015 Oct;72[10]:1132-8).
There is a hormonal rationale for exclusive breastfeeding exerting a protective effect on MS: With exclusive breastfeeding comes more frequent, intense suckling, with more profound elevations in prolactin, and larger drops in follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. All these hormonal changes work together to produce more prolonged amenorrhea and anovulation, Dr. Langer-Gould said, with potentially beneficial immunologic effects.
When other, more general maternal and infant health benefits of breastfeeding also are taken into account, there’s strong evidence for the benefits of breastfeeding for women with MS whose medication profile allows them to breastfeed, she said.
However, the “treatment” effect of exclusive breastfeeding is only effective until the infant starts taking regular supplemental feedings, including the introduction of table food at around 6 months of age. “Once regular supplemental feedings are introduced, relapses return,” Dr. Langer-Gould said.
There is some suggestion that, in women without MS, prolonged breastfeeding may be associated with reduced risk of MS. In the MS Sunshine study, breastfeeding for 15 months or longer decreased the risk of later MS by 23%-53% (Nutrients. 2018 Feb 27;10[3]:268). The investigators, led by Dr. Langer-Gould, summed the total months of breastfeeding across all children, so that the 15-month threshold could be reached by breastfeeding one child for 15 months, or three children for 5 months each. “It’s a single study; I wouldn’t make too much out of it,” Dr. Langer-Gould said.
Open questions still remain, she said: “So far, no one has been able to demonstrate a clear beneficial effect in reducing the risk of postpartum relapse if they resume their DMT early in the postpartum period.” Dr. Langer-Gould noted that the literature in this area is hampered by heterogeneity and by the fact that newer, more highly active DMTs have not been well studied.
Also, the link between postpartum relapses and long-term prognosis is not completely delineated. Indirect evidence, she said, points to a postpartum relapse as being “overall, a low-impact event.”
Dr. Langer-Gould reported that she has been the site principal investigator for clinical trials sponsored by Roche and Biogen.
SOURCE: Langer-Gould A. ECTRIMS 2018, Abstract 5.
BERLIN – In the changing multiple sclerosis landscape, more women are having babies, and more are asking questions. With these women, what’s the best way to address the complicated interplay among pregnancy, relapse risk, breastfeeding, and medication resumption? A starting point is to recognize that “women with MS are very different today than they were 25 years ago,” said Annette Langer-Gould, MD, PhD. Not only have diagnostic criteria changed but also highly effective treatments now exist that were not available when the first pregnancy cohorts were studied, she pointed out, speaking at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.
The existing literature, said Dr. Langer-Gould, has addressed one controversy: “Most women with MS can have normal pregnancies – and breastfeed – without incurring harm,” though it’s true that severe rebound relapses are possible if natalizumab (Tysabri) or fingolimod (Gilenya) are stopped before pregnancy. In any case, new small-molecule MS medications need to be stopped during pregnancy and breastfeeding, she pointed out. “We didn’t have to worry about that too much when we only had injectables and monoclonal antibodies because they were larger and didn’t cross the placenta.”
Since the 1980s, the conversation about pregnancy and MS has moved from asking “Is pregnancy bad for women with MS?” to the current MS landscape, in which sicker women are able to become pregnant, Dr. Langer-Gould said, adding that how women with MS fare through pregnancy and in the postpartum period is changing over time as well. She and her colleagues’ experience with pregnancy in a cohort of women with MS in the Kaiser Permanente care system, where she is a clinical neurologist and regional research lead, revealed a relapse rate of 8.4%. “So it was pretty rare for a woman to have a relapse during pregnancy,” Dr. Langer-Gould said.
Most women with MS who become pregnant, whether their care is received in a referral center or is community based, are now doing so while on a disease-modifying therapy (DMT), Dr. Langer-Gould said. On these highly effective treatments, “women who were too sick to get pregnant are now well controlled and having babies.”
As more women with MS become pregnant, more conversations about breastfeeding will inevitably crop up, she said. And the discussion about breastfeeding has now begun to acknowledge the “strong benefits to mom and the baby of not just breastfeeding, but longer breastfeeding,” as well.
“Because of this baby-friendly push in a lot of hospitals in the United States, where they’re trying to encourage all women to breastfeed,” a full 87% of women breastfed their infants at least some of the time, and over a third of women (35%) breastfed exclusively for at least 2 months, Dr. Langer-Gould said.
“There’s no one clear explanation of why the women seem to be healthier and doing better through pregnancy as a group, but it’s probably a combination of having milder disease, breastfeeding more, and they’ve got better controlled disease before pregnancy,” she said.
At least eight studies to date have examined the relationship between postpartum MS relapses and breastfeeding, Dr. Langer-Gould said.
“The thing to take away ... is that, even though we’ve studied this many, many times, no one can show that it’s harmful,” she said. For mothers who want to breastfeed, “you can support them in the breastfeeding choice, because they are not going to have more severe disease because of that.”
Whether breastfeeding is exclusive or not has not always been tracked in studies of childbearing women with MS, but when it was captured in the data, exclusive breastfeeding has exerted a protective effect, with about a 50% reduction in risk for postpartum relapse seen in one study (JAMA Neurol. 2015 Oct;72[10]:1132-8).
There is a hormonal rationale for exclusive breastfeeding exerting a protective effect on MS: With exclusive breastfeeding comes more frequent, intense suckling, with more profound elevations in prolactin, and larger drops in follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. All these hormonal changes work together to produce more prolonged amenorrhea and anovulation, Dr. Langer-Gould said, with potentially beneficial immunologic effects.
When other, more general maternal and infant health benefits of breastfeeding also are taken into account, there’s strong evidence for the benefits of breastfeeding for women with MS whose medication profile allows them to breastfeed, she said.
However, the “treatment” effect of exclusive breastfeeding is only effective until the infant starts taking regular supplemental feedings, including the introduction of table food at around 6 months of age. “Once regular supplemental feedings are introduced, relapses return,” Dr. Langer-Gould said.
There is some suggestion that, in women without MS, prolonged breastfeeding may be associated with reduced risk of MS. In the MS Sunshine study, breastfeeding for 15 months or longer decreased the risk of later MS by 23%-53% (Nutrients. 2018 Feb 27;10[3]:268). The investigators, led by Dr. Langer-Gould, summed the total months of breastfeeding across all children, so that the 15-month threshold could be reached by breastfeeding one child for 15 months, or three children for 5 months each. “It’s a single study; I wouldn’t make too much out of it,” Dr. Langer-Gould said.
Open questions still remain, she said: “So far, no one has been able to demonstrate a clear beneficial effect in reducing the risk of postpartum relapse if they resume their DMT early in the postpartum period.” Dr. Langer-Gould noted that the literature in this area is hampered by heterogeneity and by the fact that newer, more highly active DMTs have not been well studied.
Also, the link between postpartum relapses and long-term prognosis is not completely delineated. Indirect evidence, she said, points to a postpartum relapse as being “overall, a low-impact event.”
Dr. Langer-Gould reported that she has been the site principal investigator for clinical trials sponsored by Roche and Biogen.
SOURCE: Langer-Gould A. ECTRIMS 2018, Abstract 5.
REPORTING FROM ECTRIMS 2018
Redo carotid endarterectomy is more risky than previously estimated
NEW YORK – It is well known that reoperative carotid endarterectomy can be technically challenging because of the scarring left from the initial procedure, but an analysis of a large database presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation also revealed that the risk of complications, particularly stroke, is greater.
When “redo” carotid endarterectomies were compared with the index primary procedure collected in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the odds ratio for stroke was several times greater (odds ratio, 3.71; P = .002) on univariate analysis, reported Jeffrey J. Siracuse, MD, associate professor of surgery and radiology at Boston University.
Previous single-center reports of redo endarterectomies “showed terrific results, really no perioperative stroke or morbidity, but this is older data from a different era,” said Dr. Siracuse, who undertook this study to determine whether “real-world” data would tell a different story.
In this study, 75,943 primary carotid endarterectomies and 140 redo procedures were identified in the ACS NSQIP database and compared. The redo population had a significantly higher incidence of end-stage renal disease (3.6% vs. 1.1%; P = .004), but history of stroke, whether with deficit (20.8% vs. 15.4%) or without (11.5% vs. 9.1%), was numerically higher among those undergoing a primary procedure even though these differences did not reach statistical significance. Baseline demographics and comorbidities were otherwise similar.
Presumably because of the difficulty of recanalizing scarred tissue, the mean procedure time for redos was longer than that for the primary procedures (137 vs. 49 minutes; P less than .001), but there were no significant differences in the rate of surgical site infections (0.7% vs. 0.3%; P = .482), return to the operating room (3.6% vs. 4%; P = .853), or 30-day readmissions (2.1% vs. 6.9%; P = .810) for the redo and index procedures, respectively.
Although perioperative MI rates were higher in the redo group (2.1%) than in the primary endarterectomy group (0.9%), this difference did not reach statistical significance (P = .125). However, a multivariate analysis associated redo carotid endarterectomy procedures with a nearly threefold increase in risk of a composite of major adverse cardiovascular events when compared on a multivariate analysis (OR, 2.76; P = .007), Dr. Siracuse reported.
For the surgeons considering a redo carotid endarterectomy, these data “inform a risk-benefit analysis,” according to Dr. Siracuse, but he also said that redo procedures still should be considered a viable strategy when considered in the context of other options.
Presenting a case he performed just prior to the VEITHsymposium, Dr. Siracuse displayed CT images that showed internal and common carotids with more than 75% stenosis in an 80-year-old women 7 years after a primary carotid endarterectomy. The tight stenoses and the evidence of substantial intra-arterial debris were concerns, but a decision to perform a redo endarterectomy was reached after other options, including stenting, were considered.
“She did great. She went home and has had no more symptoms,” Dr. Siracuse reported. “The point is you still have to take these [potential redo endarterectomies] on a case-by case basis.”
Dr. Siracuse reported he had no financial relationships relevant to this study.
NEW YORK – It is well known that reoperative carotid endarterectomy can be technically challenging because of the scarring left from the initial procedure, but an analysis of a large database presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation also revealed that the risk of complications, particularly stroke, is greater.
When “redo” carotid endarterectomies were compared with the index primary procedure collected in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the odds ratio for stroke was several times greater (odds ratio, 3.71; P = .002) on univariate analysis, reported Jeffrey J. Siracuse, MD, associate professor of surgery and radiology at Boston University.
Previous single-center reports of redo endarterectomies “showed terrific results, really no perioperative stroke or morbidity, but this is older data from a different era,” said Dr. Siracuse, who undertook this study to determine whether “real-world” data would tell a different story.
In this study, 75,943 primary carotid endarterectomies and 140 redo procedures were identified in the ACS NSQIP database and compared. The redo population had a significantly higher incidence of end-stage renal disease (3.6% vs. 1.1%; P = .004), but history of stroke, whether with deficit (20.8% vs. 15.4%) or without (11.5% vs. 9.1%), was numerically higher among those undergoing a primary procedure even though these differences did not reach statistical significance. Baseline demographics and comorbidities were otherwise similar.
Presumably because of the difficulty of recanalizing scarred tissue, the mean procedure time for redos was longer than that for the primary procedures (137 vs. 49 minutes; P less than .001), but there were no significant differences in the rate of surgical site infections (0.7% vs. 0.3%; P = .482), return to the operating room (3.6% vs. 4%; P = .853), or 30-day readmissions (2.1% vs. 6.9%; P = .810) for the redo and index procedures, respectively.
Although perioperative MI rates were higher in the redo group (2.1%) than in the primary endarterectomy group (0.9%), this difference did not reach statistical significance (P = .125). However, a multivariate analysis associated redo carotid endarterectomy procedures with a nearly threefold increase in risk of a composite of major adverse cardiovascular events when compared on a multivariate analysis (OR, 2.76; P = .007), Dr. Siracuse reported.
For the surgeons considering a redo carotid endarterectomy, these data “inform a risk-benefit analysis,” according to Dr. Siracuse, but he also said that redo procedures still should be considered a viable strategy when considered in the context of other options.
Presenting a case he performed just prior to the VEITHsymposium, Dr. Siracuse displayed CT images that showed internal and common carotids with more than 75% stenosis in an 80-year-old women 7 years after a primary carotid endarterectomy. The tight stenoses and the evidence of substantial intra-arterial debris were concerns, but a decision to perform a redo endarterectomy was reached after other options, including stenting, were considered.
“She did great. She went home and has had no more symptoms,” Dr. Siracuse reported. “The point is you still have to take these [potential redo endarterectomies] on a case-by case basis.”
Dr. Siracuse reported he had no financial relationships relevant to this study.
NEW YORK – It is well known that reoperative carotid endarterectomy can be technically challenging because of the scarring left from the initial procedure, but an analysis of a large database presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation also revealed that the risk of complications, particularly stroke, is greater.
When “redo” carotid endarterectomies were compared with the index primary procedure collected in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the odds ratio for stroke was several times greater (odds ratio, 3.71; P = .002) on univariate analysis, reported Jeffrey J. Siracuse, MD, associate professor of surgery and radiology at Boston University.
Previous single-center reports of redo endarterectomies “showed terrific results, really no perioperative stroke or morbidity, but this is older data from a different era,” said Dr. Siracuse, who undertook this study to determine whether “real-world” data would tell a different story.
In this study, 75,943 primary carotid endarterectomies and 140 redo procedures were identified in the ACS NSQIP database and compared. The redo population had a significantly higher incidence of end-stage renal disease (3.6% vs. 1.1%; P = .004), but history of stroke, whether with deficit (20.8% vs. 15.4%) or without (11.5% vs. 9.1%), was numerically higher among those undergoing a primary procedure even though these differences did not reach statistical significance. Baseline demographics and comorbidities were otherwise similar.
Presumably because of the difficulty of recanalizing scarred tissue, the mean procedure time for redos was longer than that for the primary procedures (137 vs. 49 minutes; P less than .001), but there were no significant differences in the rate of surgical site infections (0.7% vs. 0.3%; P = .482), return to the operating room (3.6% vs. 4%; P = .853), or 30-day readmissions (2.1% vs. 6.9%; P = .810) for the redo and index procedures, respectively.
Although perioperative MI rates were higher in the redo group (2.1%) than in the primary endarterectomy group (0.9%), this difference did not reach statistical significance (P = .125). However, a multivariate analysis associated redo carotid endarterectomy procedures with a nearly threefold increase in risk of a composite of major adverse cardiovascular events when compared on a multivariate analysis (OR, 2.76; P = .007), Dr. Siracuse reported.
For the surgeons considering a redo carotid endarterectomy, these data “inform a risk-benefit analysis,” according to Dr. Siracuse, but he also said that redo procedures still should be considered a viable strategy when considered in the context of other options.
Presenting a case he performed just prior to the VEITHsymposium, Dr. Siracuse displayed CT images that showed internal and common carotids with more than 75% stenosis in an 80-year-old women 7 years after a primary carotid endarterectomy. The tight stenoses and the evidence of substantial intra-arterial debris were concerns, but a decision to perform a redo endarterectomy was reached after other options, including stenting, were considered.
“She did great. She went home and has had no more symptoms,” Dr. Siracuse reported. “The point is you still have to take these [potential redo endarterectomies] on a case-by case basis.”
Dr. Siracuse reported he had no financial relationships relevant to this study.
REPORTING FROM VEITHSYMPOSIUM
Key clinical point:
Major finding: The odds ratio for stroke is 3.71 times higher (P = .002) with redo than with primary carotid endarterectomy.
Study details: Multivariate retrospective database analysis.
Disclosures: Dr. Siracuse reported he had no financial relationships relevant to this study.
Fewer insured may have helped slow health spending growth in 2017
Health care spending as a percentage of gross domestic product remained relatively stable in 2017, despite a slowdown in the growth of spending.
Total health care spending in the United States was $3.5 trillion in 2017, an increase of 3.9% from 2016, according to data released Dec. 6 by the Centers for Medicare & Medicaid Services.
The growth rate was down from that of 2016 (4.8%) but similar to growth rates experienced during 2008-2013, according to the research article in Health Affairs.
“The slower growth in health care spending in 2017 resulted primarily from slower growth in hospital care, physician and clinical services, and retail prescription drugs, with residual use and intensity of these goods and services contributing substantially to the trend,” Anne B. Martin, an economist in the CMS Office of the Actuary’s National Health Statistics Group, and her colleagues wrote.
The report notes that slower growth in the use and intensity of health care goods and services in 2017 “may have been affected by slower growth in overall health insurance enrollment, as the insured share of the population fell from 91.1% in 2016 to 90.9% in 2017.”
Spending on hospital care increased 4.6% to $1.1 trillion in 2017 and accounted for 33% of total health care spending; however, growth was slower than in the previous year (5.6%). Ms. Martin and her colleagues noted that growth in outpatient visits slowed while growth in inpatient days increased at about the same rate and prices in hospital care grew in 2017 to 1.7% from 1.2% in the previous year.
Spending on physician and clinical services grew 4.2% in 2017 to $694.3 billion and accounted for 20% of total health care spending. The growth rate is down from the previous year (5.6%) and a recent peak of 6% in 2015.
“Although spending growth for both physician services and clinical services slowed in 2017, the growth rate for the latter (5.0%) continued to out pace the rate for the former (3.9%), as spending for most types of outpatient care centers contributed to the stronger growth in spending for clinical services,” Ms. Martin and her colleagues reported.
They attributed the slowdown to non-price factors, such as slower growth in the use and intensity of physician and clinical services, although price growth for physician and clinical services increased 0.4% in 2017, up from 0.2% in 2016.
Spending on retail prescription drugs grew 0.4% in 2017 to $333.4 billion and accounted for 10% of total national health spending. It is the slowest growth rate increase since 2012, a year that saw a number of blockbuster drugs lose patent protection. This was down from a growth rate of 2.3% in 2016 and down from recent rates of 12.4% in 2014 and 8.9% in 2015.
“Slower growth in non-price factors, such as the use and mix of retail prescription drugs – and, to a lesser extent, in retail prescription drug prices – contributed to the slower overall growth in retail prescription drug spending in 2017,” according to the authors. Key factors included slower growth in the number of prescriptions dispensed, the continued shift to lower-cost generics, and slower growth in the volume of high-cost drugs, particularly those used to treat hepatitis C. Price decreases in generics and lower increases for existing brand-name drugs also contributed to the lower spending growth in 2017.
Ms. Martin and her colleagues highlighted the slower growth rate in the number of prescriptions (1.8% in 2017, down from 2.3% in 2016) “resulted in large part from a decline in the number of prescriptions dispensed for drugs used to treat pain.”
Medicare spending, which represents 20% of all national health care spending in 2017 ($705.9 billion), grew 4.2%, a slight decline from the 4.3% growth in 2016. Enrollment growth slowed slightly to 2.5% in 2017 from 2.7% in the previous year, while in the same time frame, per-enrollee expenditures increased slightly to 1.7% from 1.6%. Slower growth in fee-for-service Medicare spending was offset by faster growth in spending by Medicare private health plans.
Medicaid spending reached $581.9 billion (17% of national health care spending), and the growth rate slowed for the third straight year, increasing 2.9% in 2017 versus 4.2% in 2016. The slower growth “was influenced by a deceleration in enrollment growth and a reduction in the Medicaid net cost of health insurance as the federal government recovered payments from managed care organizations based on their favorable prior-period experience,” the authors stated. Enrollment growth has been decelerating following a peak of growth of 11.9% in 2014 because of states that elected to expand Medicaid eligibility, which was followed by 3 years of slower growth rates of 4.9%, 3.0% and 2.0% in 2015, 2016, and 2017, respectively. Per-enrollee spending also slowed to 0.9% growth in 2017 from a rate of 1.2% in 2016, attributed to “the decline in government administration and the net cost of insurance.”
SOURCE: Martin A et al. Health Aff. 2018. doi: 10.1377/hlthaff.2018.05085.
Health care spending as a percentage of gross domestic product remained relatively stable in 2017, despite a slowdown in the growth of spending.
Total health care spending in the United States was $3.5 trillion in 2017, an increase of 3.9% from 2016, according to data released Dec. 6 by the Centers for Medicare & Medicaid Services.
The growth rate was down from that of 2016 (4.8%) but similar to growth rates experienced during 2008-2013, according to the research article in Health Affairs.
“The slower growth in health care spending in 2017 resulted primarily from slower growth in hospital care, physician and clinical services, and retail prescription drugs, with residual use and intensity of these goods and services contributing substantially to the trend,” Anne B. Martin, an economist in the CMS Office of the Actuary’s National Health Statistics Group, and her colleagues wrote.
The report notes that slower growth in the use and intensity of health care goods and services in 2017 “may have been affected by slower growth in overall health insurance enrollment, as the insured share of the population fell from 91.1% in 2016 to 90.9% in 2017.”
Spending on hospital care increased 4.6% to $1.1 trillion in 2017 and accounted for 33% of total health care spending; however, growth was slower than in the previous year (5.6%). Ms. Martin and her colleagues noted that growth in outpatient visits slowed while growth in inpatient days increased at about the same rate and prices in hospital care grew in 2017 to 1.7% from 1.2% in the previous year.
Spending on physician and clinical services grew 4.2% in 2017 to $694.3 billion and accounted for 20% of total health care spending. The growth rate is down from the previous year (5.6%) and a recent peak of 6% in 2015.
“Although spending growth for both physician services and clinical services slowed in 2017, the growth rate for the latter (5.0%) continued to out pace the rate for the former (3.9%), as spending for most types of outpatient care centers contributed to the stronger growth in spending for clinical services,” Ms. Martin and her colleagues reported.
They attributed the slowdown to non-price factors, such as slower growth in the use and intensity of physician and clinical services, although price growth for physician and clinical services increased 0.4% in 2017, up from 0.2% in 2016.
Spending on retail prescription drugs grew 0.4% in 2017 to $333.4 billion and accounted for 10% of total national health spending. It is the slowest growth rate increase since 2012, a year that saw a number of blockbuster drugs lose patent protection. This was down from a growth rate of 2.3% in 2016 and down from recent rates of 12.4% in 2014 and 8.9% in 2015.
“Slower growth in non-price factors, such as the use and mix of retail prescription drugs – and, to a lesser extent, in retail prescription drug prices – contributed to the slower overall growth in retail prescription drug spending in 2017,” according to the authors. Key factors included slower growth in the number of prescriptions dispensed, the continued shift to lower-cost generics, and slower growth in the volume of high-cost drugs, particularly those used to treat hepatitis C. Price decreases in generics and lower increases for existing brand-name drugs also contributed to the lower spending growth in 2017.
Ms. Martin and her colleagues highlighted the slower growth rate in the number of prescriptions (1.8% in 2017, down from 2.3% in 2016) “resulted in large part from a decline in the number of prescriptions dispensed for drugs used to treat pain.”
Medicare spending, which represents 20% of all national health care spending in 2017 ($705.9 billion), grew 4.2%, a slight decline from the 4.3% growth in 2016. Enrollment growth slowed slightly to 2.5% in 2017 from 2.7% in the previous year, while in the same time frame, per-enrollee expenditures increased slightly to 1.7% from 1.6%. Slower growth in fee-for-service Medicare spending was offset by faster growth in spending by Medicare private health plans.
Medicaid spending reached $581.9 billion (17% of national health care spending), and the growth rate slowed for the third straight year, increasing 2.9% in 2017 versus 4.2% in 2016. The slower growth “was influenced by a deceleration in enrollment growth and a reduction in the Medicaid net cost of health insurance as the federal government recovered payments from managed care organizations based on their favorable prior-period experience,” the authors stated. Enrollment growth has been decelerating following a peak of growth of 11.9% in 2014 because of states that elected to expand Medicaid eligibility, which was followed by 3 years of slower growth rates of 4.9%, 3.0% and 2.0% in 2015, 2016, and 2017, respectively. Per-enrollee spending also slowed to 0.9% growth in 2017 from a rate of 1.2% in 2016, attributed to “the decline in government administration and the net cost of insurance.”
SOURCE: Martin A et al. Health Aff. 2018. doi: 10.1377/hlthaff.2018.05085.
Health care spending as a percentage of gross domestic product remained relatively stable in 2017, despite a slowdown in the growth of spending.
Total health care spending in the United States was $3.5 trillion in 2017, an increase of 3.9% from 2016, according to data released Dec. 6 by the Centers for Medicare & Medicaid Services.
The growth rate was down from that of 2016 (4.8%) but similar to growth rates experienced during 2008-2013, according to the research article in Health Affairs.
“The slower growth in health care spending in 2017 resulted primarily from slower growth in hospital care, physician and clinical services, and retail prescription drugs, with residual use and intensity of these goods and services contributing substantially to the trend,” Anne B. Martin, an economist in the CMS Office of the Actuary’s National Health Statistics Group, and her colleagues wrote.
The report notes that slower growth in the use and intensity of health care goods and services in 2017 “may have been affected by slower growth in overall health insurance enrollment, as the insured share of the population fell from 91.1% in 2016 to 90.9% in 2017.”
Spending on hospital care increased 4.6% to $1.1 trillion in 2017 and accounted for 33% of total health care spending; however, growth was slower than in the previous year (5.6%). Ms. Martin and her colleagues noted that growth in outpatient visits slowed while growth in inpatient days increased at about the same rate and prices in hospital care grew in 2017 to 1.7% from 1.2% in the previous year.
Spending on physician and clinical services grew 4.2% in 2017 to $694.3 billion and accounted for 20% of total health care spending. The growth rate is down from the previous year (5.6%) and a recent peak of 6% in 2015.
“Although spending growth for both physician services and clinical services slowed in 2017, the growth rate for the latter (5.0%) continued to out pace the rate for the former (3.9%), as spending for most types of outpatient care centers contributed to the stronger growth in spending for clinical services,” Ms. Martin and her colleagues reported.
They attributed the slowdown to non-price factors, such as slower growth in the use and intensity of physician and clinical services, although price growth for physician and clinical services increased 0.4% in 2017, up from 0.2% in 2016.
Spending on retail prescription drugs grew 0.4% in 2017 to $333.4 billion and accounted for 10% of total national health spending. It is the slowest growth rate increase since 2012, a year that saw a number of blockbuster drugs lose patent protection. This was down from a growth rate of 2.3% in 2016 and down from recent rates of 12.4% in 2014 and 8.9% in 2015.
“Slower growth in non-price factors, such as the use and mix of retail prescription drugs – and, to a lesser extent, in retail prescription drug prices – contributed to the slower overall growth in retail prescription drug spending in 2017,” according to the authors. Key factors included slower growth in the number of prescriptions dispensed, the continued shift to lower-cost generics, and slower growth in the volume of high-cost drugs, particularly those used to treat hepatitis C. Price decreases in generics and lower increases for existing brand-name drugs also contributed to the lower spending growth in 2017.
Ms. Martin and her colleagues highlighted the slower growth rate in the number of prescriptions (1.8% in 2017, down from 2.3% in 2016) “resulted in large part from a decline in the number of prescriptions dispensed for drugs used to treat pain.”
Medicare spending, which represents 20% of all national health care spending in 2017 ($705.9 billion), grew 4.2%, a slight decline from the 4.3% growth in 2016. Enrollment growth slowed slightly to 2.5% in 2017 from 2.7% in the previous year, while in the same time frame, per-enrollee expenditures increased slightly to 1.7% from 1.6%. Slower growth in fee-for-service Medicare spending was offset by faster growth in spending by Medicare private health plans.
Medicaid spending reached $581.9 billion (17% of national health care spending), and the growth rate slowed for the third straight year, increasing 2.9% in 2017 versus 4.2% in 2016. The slower growth “was influenced by a deceleration in enrollment growth and a reduction in the Medicaid net cost of health insurance as the federal government recovered payments from managed care organizations based on their favorable prior-period experience,” the authors stated. Enrollment growth has been decelerating following a peak of growth of 11.9% in 2014 because of states that elected to expand Medicaid eligibility, which was followed by 3 years of slower growth rates of 4.9%, 3.0% and 2.0% in 2015, 2016, and 2017, respectively. Per-enrollee spending also slowed to 0.9% growth in 2017 from a rate of 1.2% in 2016, attributed to “the decline in government administration and the net cost of insurance.”
SOURCE: Martin A et al. Health Aff. 2018. doi: 10.1377/hlthaff.2018.05085.
FROM HEALTH AFFAIRS
Key clinical point: National health care spending growth slowed to 3.9% in 2017.
Major finding: The $3.5 trillion in national health care spending represents 17.9% of GDP.
Study details: Annual analysis of national health expenditures conducted by federal actuaries.
Disclosures: Analysis conducted by the Centers for Medicaid & Medicare Services Office of the Actuary; the authors have no relevant financial conflicts of interest.
Source: Martin A et al. Health Affairs. 2018. doi: 10.1377/hlthaff.2018.05085.
Perioperative M&M similar for lobar, sublobar surgeries in early lung cancer
Though lobectomy is the long-held standard of care for people with early stage non–small cell lung cancer, a noninferiority study shows little difference in perioperative morbidity and mortality outcomes when sublobar resections are performed instead.
The study, published online in The Lancet Respiratory Medicine, compared results from 697 functionally and physically fit patients with stage I cancer randomized over a 10-year period to lobar resection (n = 357) or sublobar resection (n = 340). Patients were analyzed for morbidity and mortality outcomes at 30 and 90 days post surgery. Nasser K. Altorki, MD, of Weill Cornell Medicine–New York Presbyterian Hospital, led the study as a post hoc, exploratory analysis of CALGB/Alliance 140503, a multinational phase 3 trial whose primary outcome – still pending – is disease-free survival associated with the two different surgeries.
Dr. Altorki and his colleagues found 30- and 90-day survival to be comparable between surgery types. At 30 days, six patients in the study had died; four in the lobar resection group and two in the sublobar group (1.1% and 0.6%). At 90 days, 10 patients had died, or 1.4% of the cohort; 6 following lobar resection and 4 following sublobar resection. The between-group difference at 30 days was 0.5% (95% confidence interval, –1.1 to 2.3) and at 90 days remained 0.5% (95% CI, –1.5 to 2.6).
Similar rates of serious (grade 3 or worse) adverse advents were seen between surgery groups at 15% and 14%, respectively, and no differences were seen for cardiac or pulmonary complications. In the study, the type of sublobar approach was left to the surgeon’s discretion, and a majority of the sublobar procedures (59%) were found to comprise wedge resections, with the rest segmentectomies. Dr. Altorki and colleagues noted the high rate of wedge resections as striking, because “conventional wisdom … holds that an anatomical segmentectomy, involving individual ligation of segmental vessels and bronchi and wider parenchymal resection, is oncologically superior to nonanatomical wedge resections.” In their analysis the researchers conceded that a three-arm trial allocating patients to lobectomy, segmentectomy, or wedge resection “would have answered more precisely the posited research question,” but said that the sample size needed would have been too large.
The study was funded by the National Cancer Institute. Dr. Altorki reported a research grant from AstraZeneca unrelated to the study; two more coauthors disclosed funding from pharmaceutical or device manufacturers, and an additional 17 coauthors listed no competing interests.
SOURCE: Altorki NK et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9 .
Though lobectomy is the long-held standard of care for people with early stage non–small cell lung cancer, a noninferiority study shows little difference in perioperative morbidity and mortality outcomes when sublobar resections are performed instead.
The study, published online in The Lancet Respiratory Medicine, compared results from 697 functionally and physically fit patients with stage I cancer randomized over a 10-year period to lobar resection (n = 357) or sublobar resection (n = 340). Patients were analyzed for morbidity and mortality outcomes at 30 and 90 days post surgery. Nasser K. Altorki, MD, of Weill Cornell Medicine–New York Presbyterian Hospital, led the study as a post hoc, exploratory analysis of CALGB/Alliance 140503, a multinational phase 3 trial whose primary outcome – still pending – is disease-free survival associated with the two different surgeries.
Dr. Altorki and his colleagues found 30- and 90-day survival to be comparable between surgery types. At 30 days, six patients in the study had died; four in the lobar resection group and two in the sublobar group (1.1% and 0.6%). At 90 days, 10 patients had died, or 1.4% of the cohort; 6 following lobar resection and 4 following sublobar resection. The between-group difference at 30 days was 0.5% (95% confidence interval, –1.1 to 2.3) and at 90 days remained 0.5% (95% CI, –1.5 to 2.6).
Similar rates of serious (grade 3 or worse) adverse advents were seen between surgery groups at 15% and 14%, respectively, and no differences were seen for cardiac or pulmonary complications. In the study, the type of sublobar approach was left to the surgeon’s discretion, and a majority of the sublobar procedures (59%) were found to comprise wedge resections, with the rest segmentectomies. Dr. Altorki and colleagues noted the high rate of wedge resections as striking, because “conventional wisdom … holds that an anatomical segmentectomy, involving individual ligation of segmental vessels and bronchi and wider parenchymal resection, is oncologically superior to nonanatomical wedge resections.” In their analysis the researchers conceded that a three-arm trial allocating patients to lobectomy, segmentectomy, or wedge resection “would have answered more precisely the posited research question,” but said that the sample size needed would have been too large.
The study was funded by the National Cancer Institute. Dr. Altorki reported a research grant from AstraZeneca unrelated to the study; two more coauthors disclosed funding from pharmaceutical or device manufacturers, and an additional 17 coauthors listed no competing interests.
SOURCE: Altorki NK et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9 .
Though lobectomy is the long-held standard of care for people with early stage non–small cell lung cancer, a noninferiority study shows little difference in perioperative morbidity and mortality outcomes when sublobar resections are performed instead.
The study, published online in The Lancet Respiratory Medicine, compared results from 697 functionally and physically fit patients with stage I cancer randomized over a 10-year period to lobar resection (n = 357) or sublobar resection (n = 340). Patients were analyzed for morbidity and mortality outcomes at 30 and 90 days post surgery. Nasser K. Altorki, MD, of Weill Cornell Medicine–New York Presbyterian Hospital, led the study as a post hoc, exploratory analysis of CALGB/Alliance 140503, a multinational phase 3 trial whose primary outcome – still pending – is disease-free survival associated with the two different surgeries.
Dr. Altorki and his colleagues found 30- and 90-day survival to be comparable between surgery types. At 30 days, six patients in the study had died; four in the lobar resection group and two in the sublobar group (1.1% and 0.6%). At 90 days, 10 patients had died, or 1.4% of the cohort; 6 following lobar resection and 4 following sublobar resection. The between-group difference at 30 days was 0.5% (95% confidence interval, –1.1 to 2.3) and at 90 days remained 0.5% (95% CI, –1.5 to 2.6).
Similar rates of serious (grade 3 or worse) adverse advents were seen between surgery groups at 15% and 14%, respectively, and no differences were seen for cardiac or pulmonary complications. In the study, the type of sublobar approach was left to the surgeon’s discretion, and a majority of the sublobar procedures (59%) were found to comprise wedge resections, with the rest segmentectomies. Dr. Altorki and colleagues noted the high rate of wedge resections as striking, because “conventional wisdom … holds that an anatomical segmentectomy, involving individual ligation of segmental vessels and bronchi and wider parenchymal resection, is oncologically superior to nonanatomical wedge resections.” In their analysis the researchers conceded that a three-arm trial allocating patients to lobectomy, segmentectomy, or wedge resection “would have answered more precisely the posited research question,” but said that the sample size needed would have been too large.
The study was funded by the National Cancer Institute. Dr. Altorki reported a research grant from AstraZeneca unrelated to the study; two more coauthors disclosed funding from pharmaceutical or device manufacturers, and an additional 17 coauthors listed no competing interests.
SOURCE: Altorki NK et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9 .
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Patients with 30 and 90 days post surgery.
Major finding: Mortality at 30 days and 90 days was 0.5% for both trial groups and serious adverse advents were similar between groups.
Study details: A post hoc analysis from a multinational trial randomizing about 700 stage I NSCLC patients to lobar or sublobar surgery
Disclosures: National Cancer Institute sponsored the study; three authors including the lead author reported financial ties to manufacturers.
Source: Altorki et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9.
Atezolizumab combination regimen approved for advanced non-squamous NSCLC
The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations.
Approval was based on greater overall survival (OS) among patients receiving the four drug combination, compared with patients who did not receive the checkpoint inhibitor but received the other three drugs in the randomized IMpower150 trial.
For the trial, 1,202 patients with metastatic NSq NSCLC were randomized to three arms for first-line treatment:
• atezolizumab, carboplatin, paclitaxel, and bevacizumab (4-drug regimen);
• atezolizumab, carboplatin and paclitaxel (3-drug regimen); or
• carboplatin, paclitaxel, and bevacizumab (control arm).
Among patients with NSq NSCLC without an EGFR or ALK mutation (87%), the estimated median OS was 19.2 months for patients receiving the 4-drug regimen and 14.7 months for those in the control arm (hazard ratio [HR] 0.78; 95% CI: 0.64, 0.96; P = .016), the FDA said in a press statement announcing the approval.
The median progression-free survival was 8.5 months for patients receiving the 4-drug regimen and 7.0 months for those in the control arm (HR 0.71; 95% CI 0.59, 0.85; P = .0002). The overall response rates were 55% in the 4-drug arm and 42% in the control arm. There were no significant differences in OS or final progression-free survival between the 3-drug arm containing atezolizumab and the control arm.
The most common adverse reactions with atezolizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Treatment with atezolizumab was discontinued in 15% of patients due to adverse reactions, the most common reason being pneumonitis.
The recommended atezolizumab dose is 1,200 mg intravenously over 60 minutes every 3 weeks, the FDA said.
The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations.
Approval was based on greater overall survival (OS) among patients receiving the four drug combination, compared with patients who did not receive the checkpoint inhibitor but received the other three drugs in the randomized IMpower150 trial.
For the trial, 1,202 patients with metastatic NSq NSCLC were randomized to three arms for first-line treatment:
• atezolizumab, carboplatin, paclitaxel, and bevacizumab (4-drug regimen);
• atezolizumab, carboplatin and paclitaxel (3-drug regimen); or
• carboplatin, paclitaxel, and bevacizumab (control arm).
Among patients with NSq NSCLC without an EGFR or ALK mutation (87%), the estimated median OS was 19.2 months for patients receiving the 4-drug regimen and 14.7 months for those in the control arm (hazard ratio [HR] 0.78; 95% CI: 0.64, 0.96; P = .016), the FDA said in a press statement announcing the approval.
The median progression-free survival was 8.5 months for patients receiving the 4-drug regimen and 7.0 months for those in the control arm (HR 0.71; 95% CI 0.59, 0.85; P = .0002). The overall response rates were 55% in the 4-drug arm and 42% in the control arm. There were no significant differences in OS or final progression-free survival between the 3-drug arm containing atezolizumab and the control arm.
The most common adverse reactions with atezolizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Treatment with atezolizumab was discontinued in 15% of patients due to adverse reactions, the most common reason being pneumonitis.
The recommended atezolizumab dose is 1,200 mg intravenously over 60 minutes every 3 weeks, the FDA said.
The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations.
Approval was based on greater overall survival (OS) among patients receiving the four drug combination, compared with patients who did not receive the checkpoint inhibitor but received the other three drugs in the randomized IMpower150 trial.
For the trial, 1,202 patients with metastatic NSq NSCLC were randomized to three arms for first-line treatment:
• atezolizumab, carboplatin, paclitaxel, and bevacizumab (4-drug regimen);
• atezolizumab, carboplatin and paclitaxel (3-drug regimen); or
• carboplatin, paclitaxel, and bevacizumab (control arm).
Among patients with NSq NSCLC without an EGFR or ALK mutation (87%), the estimated median OS was 19.2 months for patients receiving the 4-drug regimen and 14.7 months for those in the control arm (hazard ratio [HR] 0.78; 95% CI: 0.64, 0.96; P = .016), the FDA said in a press statement announcing the approval.
The median progression-free survival was 8.5 months for patients receiving the 4-drug regimen and 7.0 months for those in the control arm (HR 0.71; 95% CI 0.59, 0.85; P = .0002). The overall response rates were 55% in the 4-drug arm and 42% in the control arm. There were no significant differences in OS or final progression-free survival between the 3-drug arm containing atezolizumab and the control arm.
The most common adverse reactions with atezolizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Treatment with atezolizumab was discontinued in 15% of patients due to adverse reactions, the most common reason being pneumonitis.
The recommended atezolizumab dose is 1,200 mg intravenously over 60 minutes every 3 weeks, the FDA said.
Extended anastrozole improves DFS, distant DFS
SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).
After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.
The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.
“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).
Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.
Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.
Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.
The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.
Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.
SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.
SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).
After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.
The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.
“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).
Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.
Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.
Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.
The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.
Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.
SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.
SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).
After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.
The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.
“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).
Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.
Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.
Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.
The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.
Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.
SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.
REPORTING FROM SABCS 2018
Key clinical point: Extending treatment with adjuvant anastrozole to 10 years improves disease free survival and distant DFS in HR+ breast cancer.
Major finding: DFS was 91.9% in patients who continued anastrozole versus 84.4% in those who stopped anastrozole after the initial 5 years (hazard ratio, 0.548; P = .0004).
Study details: A prospective, randomized, open-label, phase 3 study of 1,683 patients.
Disclosures: Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis, and Ezai.
Source: Ohtani S et al. SABCS 2018, Abstract GS3-04.