User login
Nonalcoholic fatty liver disease accelerates brain aging
TORONTO – Nonalcoholic fatty liver disease seems to accelerate physical brain aging by up to 7 years, according to a new subanalysis of the ongoing Framingham Heart Study.
However, while finding that the liver disorder directly endangers brains, the study also offers hope, Galit Weinstein, PhD, said at the Alzheimer’s Association International Conference 2016. “If indeed nonalcoholic fatty liver disease is a risk factor for brain aging and subsequent dementia, then it is a modifiable one,” said Dr. Weinstein of Boston University. “We have reason to hope that NAFLD remission could possibly improve cognitive outcomes” as patients age.
For this study, the researchers assessed the presence of NAFLD by abdominal CT scans and white-matter hyperintensities and brain volume (total, frontal, and hippocampal) by MRI. The resulting associations were then adjusted for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, current smoking, diabetes, history of cardiovascular disease, physical activity, insulin resistance, and C-reactive protein.
There were no significant associations with white-matter hyperintensities or with hippocampal volume, but the researches did find a significant association with total brain volume: Even after adjustment for all of the covariates, patients with NAFLD had smaller-than-normal brains for their age. This can be seen as a pathologic acceleration of the brain aging process, Dr. Weinstein said.
The finding was most striking among the youngest subjects, she said, accounting for about a 7-year advance in brain aging for those younger than 60 years. Older patients with NAFLD showed about a 2-year advance in brain aging.
The effect is probably mediated by the liver’s complex interplay in metabolism and vascular functions, Dr. Weinstein said.
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
TORONTO – Nonalcoholic fatty liver disease seems to accelerate physical brain aging by up to 7 years, according to a new subanalysis of the ongoing Framingham Heart Study.
However, while finding that the liver disorder directly endangers brains, the study also offers hope, Galit Weinstein, PhD, said at the Alzheimer’s Association International Conference 2016. “If indeed nonalcoholic fatty liver disease is a risk factor for brain aging and subsequent dementia, then it is a modifiable one,” said Dr. Weinstein of Boston University. “We have reason to hope that NAFLD remission could possibly improve cognitive outcomes” as patients age.
For this study, the researchers assessed the presence of NAFLD by abdominal CT scans and white-matter hyperintensities and brain volume (total, frontal, and hippocampal) by MRI. The resulting associations were then adjusted for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, current smoking, diabetes, history of cardiovascular disease, physical activity, insulin resistance, and C-reactive protein.
There were no significant associations with white-matter hyperintensities or with hippocampal volume, but the researches did find a significant association with total brain volume: Even after adjustment for all of the covariates, patients with NAFLD had smaller-than-normal brains for their age. This can be seen as a pathologic acceleration of the brain aging process, Dr. Weinstein said.
The finding was most striking among the youngest subjects, she said, accounting for about a 7-year advance in brain aging for those younger than 60 years. Older patients with NAFLD showed about a 2-year advance in brain aging.
The effect is probably mediated by the liver’s complex interplay in metabolism and vascular functions, Dr. Weinstein said.
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
TORONTO – Nonalcoholic fatty liver disease seems to accelerate physical brain aging by up to 7 years, according to a new subanalysis of the ongoing Framingham Heart Study.
However, while finding that the liver disorder directly endangers brains, the study also offers hope, Galit Weinstein, PhD, said at the Alzheimer’s Association International Conference 2016. “If indeed nonalcoholic fatty liver disease is a risk factor for brain aging and subsequent dementia, then it is a modifiable one,” said Dr. Weinstein of Boston University. “We have reason to hope that NAFLD remission could possibly improve cognitive outcomes” as patients age.
For this study, the researchers assessed the presence of NAFLD by abdominal CT scans and white-matter hyperintensities and brain volume (total, frontal, and hippocampal) by MRI. The resulting associations were then adjusted for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, current smoking, diabetes, history of cardiovascular disease, physical activity, insulin resistance, and C-reactive protein.
There were no significant associations with white-matter hyperintensities or with hippocampal volume, but the researches did find a significant association with total brain volume: Even after adjustment for all of the covariates, patients with NAFLD had smaller-than-normal brains for their age. This can be seen as a pathologic acceleration of the brain aging process, Dr. Weinstein said.
The finding was most striking among the youngest subjects, she said, accounting for about a 7-year advance in brain aging for those younger than 60 years. Older patients with NAFLD showed about a 2-year advance in brain aging.
The effect is probably mediated by the liver’s complex interplay in metabolism and vascular functions, Dr. Weinstein said.
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
AT AAIC 2016
Key clinical point:
Major finding: NAFLD was associated with a 7-year advance in brain aging in people younger than 60 years.
Data source: An analysis of 906 members of the Framingham Offspring Cohort.
Disclosures: Dr. Weinstein had no financial declarations.
VIDEO: Ankylosing spondylitis problems outside the joints strike more women than men
WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.
Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.
The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”
In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.
They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.
Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.
Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).
Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.
In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).
Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.
Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.
The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”
In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.
They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.
Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.
Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).
Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.
In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).
Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Women are almost twice as likely as men to develop extra-articular manifestations of ankylosing spondylitis such as uveitis and inflammatory bowel disease, according to an analysis of patients in the Ankylosing Spondylitis Registry of Ireland.
Each of those manifestations exerts its own difficulties upon patients over and above the inflammatory back pain of the underlying disease, Gillian Fitzgerald, MD, said at the annual meeting of the American College of Rheumatology. Many patients can develop several of these separate manifestations – a circumstance that seriously affects their quality of life.
The findings of the large registry study were a bit surprising, she said during presentation of the study at a press briefing, as ankylosing spondylitis is generally thought to affect largely men. “However, this isn’t the case,” said Dr. Fitzgerald of St. James’s Hospital, Dublin. “Recent studies show that women can be affected as often as men are.”
In light of those findings, Dr. Fitzgerald and her coauthors wanted to further define the gender differences, especially with regard to extra-articular manifestations.
They accessed data on 564 patients in the registry, which was established in 2013. The majority of patients (78%) were men; the mean age was 47 years. Patients had a mean disease duration of nearly 21 years. For almost half that time (9 years) they had remained undiagnosed, Dr. Fitzgerald added. They had a mean age of about 47 years, and 78% fulfilled the modified New York criteria for ankylosing spondylitis.
Overall, extra-articular manifestations were common, with 35% having uveitis, 18% psoriasis, and 10% inflammatory bowel disease.
Uveitis was significantly more common among women (47% vs. 32%) and among those with disease duration of more than 10 years (40% vs. 22% with less than 10 years).
Inflammatory bowel disease was also significantly more common among women (16.5% vs. 8%). It wasn’t related to disease duration, but it was related to elevated baseline C-reactive protein, peptic ulcer disease, and osteoporosis.
In a multivariate regression analysis, women were 70% more likely to experience an extra-articular manifestation of the disease than were men (hazard ratio, 1.7). Having the disease for more than 10 years more than doubled the risk of an extra-articular manifestation (HR, 2.4).
Dr. Fitzgerald discussed the study’s findings in a video interview at the meeting. She had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Women were 70% more likely than men to develop an extra-articular manifestation of the disease.
Data source: The registry study comprised 564 patients.
Disclosures: Dr. Fitzgerald had no financial disclosures.
Empagliflozin first antidiabetes drug to gain cardioprotective indication
Empagliflozin is the first antidiabetes medication to be approved for reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease.
The Food and Drug Administration granted the new indication based on the EMPA-REG OUTCOME study, a postmarketing analysis that found that empagliflozin (Jardiance, Boehringer-Ingelheim) reduced the risk of cardiovascular death by 38% when added to standard-of-care type 2 diabetes therapy.
When empagliflozin was approved for type 2 diabetes in 2014, the FDA required an additional postmarketing study to examine its cardiovascular safety. The 48-month, open-label EMPA-REG enrolled more than 7,000 patients who had type 2 diabetes and a high risk of cardiovascular disease.
The study’s big surprise, however, was not empagliflozin’s safety, but its striking cardioprotective qualities. It reduced by 14% the risk of the primary endpoint, a composite of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction (N Engl J Med. 2015;373:2117-28).
When examined as individual outcomes in a secondary analysis, empagliflozin significantly reduced the risk of cardiovascular death by 38%. However, risk reductions on the other endpoints were not significant. Nevertheless, experts called empagliflozin’s cardiovascular benefit a potential game-changer for the clinical challenge of managing patients with both disorders.
But the drug barely squeaked by its June FDA approval hearing for the cardioprotective indication, receiving a split 12-11 endorsement from the Endocrinologic and Metabolic Drugs Advisory Committee. The major sticking point was that EMPA-REG was a test of empagliflozin’s cardiovascular safety, not its efficacy, and that cardiovascular death was not a prespecified endpoint.
Although there were no significant cardiovascular safety issues, empagliflozin has been associated with hypotension, serious urinary tract infection, acute kidney injury, and genital infections.
“Cardiovascular disease is a leading cause of death in adults with type 2 diabetes mellitus,” Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, wrote in a press statement. “Availability of antidiabetes therapies that can help people live longer by reducing the risk of cardiovascular death is an important advance for adults with type 2 diabetes.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
Empagliflozin is the first antidiabetes medication to be approved for reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease.
The Food and Drug Administration granted the new indication based on the EMPA-REG OUTCOME study, a postmarketing analysis that found that empagliflozin (Jardiance, Boehringer-Ingelheim) reduced the risk of cardiovascular death by 38% when added to standard-of-care type 2 diabetes therapy.
When empagliflozin was approved for type 2 diabetes in 2014, the FDA required an additional postmarketing study to examine its cardiovascular safety. The 48-month, open-label EMPA-REG enrolled more than 7,000 patients who had type 2 diabetes and a high risk of cardiovascular disease.
The study’s big surprise, however, was not empagliflozin’s safety, but its striking cardioprotective qualities. It reduced by 14% the risk of the primary endpoint, a composite of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction (N Engl J Med. 2015;373:2117-28).
When examined as individual outcomes in a secondary analysis, empagliflozin significantly reduced the risk of cardiovascular death by 38%. However, risk reductions on the other endpoints were not significant. Nevertheless, experts called empagliflozin’s cardiovascular benefit a potential game-changer for the clinical challenge of managing patients with both disorders.
But the drug barely squeaked by its June FDA approval hearing for the cardioprotective indication, receiving a split 12-11 endorsement from the Endocrinologic and Metabolic Drugs Advisory Committee. The major sticking point was that EMPA-REG was a test of empagliflozin’s cardiovascular safety, not its efficacy, and that cardiovascular death was not a prespecified endpoint.
Although there were no significant cardiovascular safety issues, empagliflozin has been associated with hypotension, serious urinary tract infection, acute kidney injury, and genital infections.
“Cardiovascular disease is a leading cause of death in adults with type 2 diabetes mellitus,” Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, wrote in a press statement. “Availability of antidiabetes therapies that can help people live longer by reducing the risk of cardiovascular death is an important advance for adults with type 2 diabetes.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
Empagliflozin is the first antidiabetes medication to be approved for reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease.
The Food and Drug Administration granted the new indication based on the EMPA-REG OUTCOME study, a postmarketing analysis that found that empagliflozin (Jardiance, Boehringer-Ingelheim) reduced the risk of cardiovascular death by 38% when added to standard-of-care type 2 diabetes therapy.
When empagliflozin was approved for type 2 diabetes in 2014, the FDA required an additional postmarketing study to examine its cardiovascular safety. The 48-month, open-label EMPA-REG enrolled more than 7,000 patients who had type 2 diabetes and a high risk of cardiovascular disease.
The study’s big surprise, however, was not empagliflozin’s safety, but its striking cardioprotective qualities. It reduced by 14% the risk of the primary endpoint, a composite of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction (N Engl J Med. 2015;373:2117-28).
When examined as individual outcomes in a secondary analysis, empagliflozin significantly reduced the risk of cardiovascular death by 38%. However, risk reductions on the other endpoints were not significant. Nevertheless, experts called empagliflozin’s cardiovascular benefit a potential game-changer for the clinical challenge of managing patients with both disorders.
But the drug barely squeaked by its June FDA approval hearing for the cardioprotective indication, receiving a split 12-11 endorsement from the Endocrinologic and Metabolic Drugs Advisory Committee. The major sticking point was that EMPA-REG was a test of empagliflozin’s cardiovascular safety, not its efficacy, and that cardiovascular death was not a prespecified endpoint.
Although there were no significant cardiovascular safety issues, empagliflozin has been associated with hypotension, serious urinary tract infection, acute kidney injury, and genital infections.
“Cardiovascular disease is a leading cause of death in adults with type 2 diabetes mellitus,” Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, wrote in a press statement. “Availability of antidiabetes therapies that can help people live longer by reducing the risk of cardiovascular death is an important advance for adults with type 2 diabetes.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
Prenatal exposure to hydroxychloroquine cuts risk of neonatal cutaneous lupus
WASHINGTON – Prenatal hydroxychloroquine reduces the risk of cutaneous neonatal lupus by 60% among the infants of women with a systemic autoimmune rheumatic disease.
The medication easily passes the placental barrier and confers significant protection to neonates born to women who have anti-Ro and anti-La antibodies, Julie Barsalou, MD, said at the annual meeting of the American College of Rheumatology.
Toll-like receptors 7 and 9 have been implicated in the initiation and maintenance of interface dermatitis, and hydroxychloroquine inhibits these receptors. In mouse studies, the drug has led to improvement of this type of dermatitis. Hydroxychloroquine also works well in treating subacute cutaneous lupus, she said, and because it can travel across the placenta, it could be an effective means of preventing this disorder in at-risk neonates.
To examine any potential benefit, Dr. Barsalou looked at three pediatric lupus databases: the SickKids NLE database from Toronto, the U.S. Research Registry for Neonatal Lupus, and the French Registry for Neonatal Lupus.
These registries include infants born to mothers with anti-Ro and/or anti-La antibodies, and a diagnosis of lupus, dermatomyositis, Sjögren’s syndrome, juvenile idiopathic arthritis, or rheumatic arthritis. No infants with cardiac neonatal lupus were included in the study.
In addition to hydroxychloroquine, Dr. Barsalou examined the use of prenatal azathioprine, nonfluorinated and fluorinated steroids, and intravenous immunoglobulin.
The cohort comprised 545 neonates born to 535 mothers. Among these, 112 developed cNLE. The remaining 433 infants were used as controls.
Mothers of both cases and controls were a mean age of 31 years. Among cases, the most common diagnosis was Sjögren’s syndrome (53%), followed by systemic lupus erythematosus (46%). Among controls, the most common maternal diagnosis was SLE (62%), followed by Sjögren’s (31%).
All mothers of cases were positive for anti-Ro antibodies; 72% were positive for anti-La antibodies. Among mothers of controls, 99% had anti-Ro antibodies and 48% had anti-La antibodies.
Mothers of cases took hydroxychloroquine (17%), fluorinated steroids (6%), and nonfluorinated steroids with or without azathioprine (28%). Mothers of controls took hydroxychloroquine (34%), fluorinated steroids (4%), and nonfluorinated steroids with or without azathioprine (44%),
There were significantly more female than male infants in the case group (65%). The median age at rash onset was 6 weeks.
Dr. Barsalou performed several multivariate analyses on the entire cohort, as well as two subgroup analyses: one on infants who developed the cNLE rash within the first 4 weeks of life and one on only the infants of mothers with SLE.
In the primary analysis, maternal anti-Ro and anti-La antibodies more than doubled the risk of an infant developing cNLE (odds ratio, 2.5). The use of hydroxychloroquine decreased this risk by 60% (OR, 0.4). Being a female infant increased the risk by 70% (OR, 1.7).
In the group of infants with early-onset rash, maternal anti-La antibodies more than tripled the risk (OR, 3.5), while the use of hydroxychloroquine decreased the risk by 80% (OR, 0.2).
Among the infants born to women with SLE, concomitant secondary Sjögren’s syndrome increased the risk of cNLE by more than threefold (OR, 3.5). Anti-La antibodies more than doubled the risk (OR, 2.5), and the use of hydroxychloroquine decreased it by 60% (OR, 0.4).
“This is the first study to address the prevention of cutaneous neonatal lupus,” Dr. Barsalou said. “We found that prenatal exposure to hydroxychloroquine is likely protective.”
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Prenatal hydroxychloroquine reduces the risk of cutaneous neonatal lupus by 60% among the infants of women with a systemic autoimmune rheumatic disease.
The medication easily passes the placental barrier and confers significant protection to neonates born to women who have anti-Ro and anti-La antibodies, Julie Barsalou, MD, said at the annual meeting of the American College of Rheumatology.
Toll-like receptors 7 and 9 have been implicated in the initiation and maintenance of interface dermatitis, and hydroxychloroquine inhibits these receptors. In mouse studies, the drug has led to improvement of this type of dermatitis. Hydroxychloroquine also works well in treating subacute cutaneous lupus, she said, and because it can travel across the placenta, it could be an effective means of preventing this disorder in at-risk neonates.
To examine any potential benefit, Dr. Barsalou looked at three pediatric lupus databases: the SickKids NLE database from Toronto, the U.S. Research Registry for Neonatal Lupus, and the French Registry for Neonatal Lupus.
These registries include infants born to mothers with anti-Ro and/or anti-La antibodies, and a diagnosis of lupus, dermatomyositis, Sjögren’s syndrome, juvenile idiopathic arthritis, or rheumatic arthritis. No infants with cardiac neonatal lupus were included in the study.
In addition to hydroxychloroquine, Dr. Barsalou examined the use of prenatal azathioprine, nonfluorinated and fluorinated steroids, and intravenous immunoglobulin.
The cohort comprised 545 neonates born to 535 mothers. Among these, 112 developed cNLE. The remaining 433 infants were used as controls.
Mothers of both cases and controls were a mean age of 31 years. Among cases, the most common diagnosis was Sjögren’s syndrome (53%), followed by systemic lupus erythematosus (46%). Among controls, the most common maternal diagnosis was SLE (62%), followed by Sjögren’s (31%).
All mothers of cases were positive for anti-Ro antibodies; 72% were positive for anti-La antibodies. Among mothers of controls, 99% had anti-Ro antibodies and 48% had anti-La antibodies.
Mothers of cases took hydroxychloroquine (17%), fluorinated steroids (6%), and nonfluorinated steroids with or without azathioprine (28%). Mothers of controls took hydroxychloroquine (34%), fluorinated steroids (4%), and nonfluorinated steroids with or without azathioprine (44%),
There were significantly more female than male infants in the case group (65%). The median age at rash onset was 6 weeks.
Dr. Barsalou performed several multivariate analyses on the entire cohort, as well as two subgroup analyses: one on infants who developed the cNLE rash within the first 4 weeks of life and one on only the infants of mothers with SLE.
In the primary analysis, maternal anti-Ro and anti-La antibodies more than doubled the risk of an infant developing cNLE (odds ratio, 2.5). The use of hydroxychloroquine decreased this risk by 60% (OR, 0.4). Being a female infant increased the risk by 70% (OR, 1.7).
In the group of infants with early-onset rash, maternal anti-La antibodies more than tripled the risk (OR, 3.5), while the use of hydroxychloroquine decreased the risk by 80% (OR, 0.2).
Among the infants born to women with SLE, concomitant secondary Sjögren’s syndrome increased the risk of cNLE by more than threefold (OR, 3.5). Anti-La antibodies more than doubled the risk (OR, 2.5), and the use of hydroxychloroquine decreased it by 60% (OR, 0.4).
“This is the first study to address the prevention of cutaneous neonatal lupus,” Dr. Barsalou said. “We found that prenatal exposure to hydroxychloroquine is likely protective.”
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Prenatal hydroxychloroquine reduces the risk of cutaneous neonatal lupus by 60% among the infants of women with a systemic autoimmune rheumatic disease.
The medication easily passes the placental barrier and confers significant protection to neonates born to women who have anti-Ro and anti-La antibodies, Julie Barsalou, MD, said at the annual meeting of the American College of Rheumatology.
Toll-like receptors 7 and 9 have been implicated in the initiation and maintenance of interface dermatitis, and hydroxychloroquine inhibits these receptors. In mouse studies, the drug has led to improvement of this type of dermatitis. Hydroxychloroquine also works well in treating subacute cutaneous lupus, she said, and because it can travel across the placenta, it could be an effective means of preventing this disorder in at-risk neonates.
To examine any potential benefit, Dr. Barsalou looked at three pediatric lupus databases: the SickKids NLE database from Toronto, the U.S. Research Registry for Neonatal Lupus, and the French Registry for Neonatal Lupus.
These registries include infants born to mothers with anti-Ro and/or anti-La antibodies, and a diagnosis of lupus, dermatomyositis, Sjögren’s syndrome, juvenile idiopathic arthritis, or rheumatic arthritis. No infants with cardiac neonatal lupus were included in the study.
In addition to hydroxychloroquine, Dr. Barsalou examined the use of prenatal azathioprine, nonfluorinated and fluorinated steroids, and intravenous immunoglobulin.
The cohort comprised 545 neonates born to 535 mothers. Among these, 112 developed cNLE. The remaining 433 infants were used as controls.
Mothers of both cases and controls were a mean age of 31 years. Among cases, the most common diagnosis was Sjögren’s syndrome (53%), followed by systemic lupus erythematosus (46%). Among controls, the most common maternal diagnosis was SLE (62%), followed by Sjögren’s (31%).
All mothers of cases were positive for anti-Ro antibodies; 72% were positive for anti-La antibodies. Among mothers of controls, 99% had anti-Ro antibodies and 48% had anti-La antibodies.
Mothers of cases took hydroxychloroquine (17%), fluorinated steroids (6%), and nonfluorinated steroids with or without azathioprine (28%). Mothers of controls took hydroxychloroquine (34%), fluorinated steroids (4%), and nonfluorinated steroids with or without azathioprine (44%),
There were significantly more female than male infants in the case group (65%). The median age at rash onset was 6 weeks.
Dr. Barsalou performed several multivariate analyses on the entire cohort, as well as two subgroup analyses: one on infants who developed the cNLE rash within the first 4 weeks of life and one on only the infants of mothers with SLE.
In the primary analysis, maternal anti-Ro and anti-La antibodies more than doubled the risk of an infant developing cNLE (odds ratio, 2.5). The use of hydroxychloroquine decreased this risk by 60% (OR, 0.4). Being a female infant increased the risk by 70% (OR, 1.7).
In the group of infants with early-onset rash, maternal anti-La antibodies more than tripled the risk (OR, 3.5), while the use of hydroxychloroquine decreased the risk by 80% (OR, 0.2).
Among the infants born to women with SLE, concomitant secondary Sjögren’s syndrome increased the risk of cNLE by more than threefold (OR, 3.5). Anti-La antibodies more than doubled the risk (OR, 2.5), and the use of hydroxychloroquine decreased it by 60% (OR, 0.4).
“This is the first study to address the prevention of cutaneous neonatal lupus,” Dr. Barsalou said. “We found that prenatal exposure to hydroxychloroquine is likely protective.”
She had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The drug was associated with a 60% decreased risk of developing the disorder.
Data source: The case-control study involved 545 infants.
Disclosures: Dr. Barsalou had no financial disclosures.
Low-dose cyclophosphamide unlikely to impair fertility in lupus patients
WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.
The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.
“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.
The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).
Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.
High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.
“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”
Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.
Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.
Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.
There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.
However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.
The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.
There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.
Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.
Dr. Tamirou and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.
The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.
“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.
The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).
Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.
High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.
“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”
Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.
Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.
Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.
There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.
However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.
The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.
There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.
Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.
Dr. Tamirou and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.
The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.
“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.
The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).
Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.
High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.
“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”
Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.
Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.
Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.
There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.
However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.
The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.
There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.
Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.
Dr. Tamirou and her colleagues had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Patients who got a cumulative cyclophosphamide dose of up to 6 grams had an anti-Mullerian hormone level close to 3 ng/mL, which is no different than the level in untreated patients.
Data source: The study comprised 155 women with systemic lupus erythematosus.
Disclosures: Dr. Tamirou and her colleagues had no financial disclosures.
Legislators commit to bipartisan support of Alzheimer’s funding
WASHINGTON – The nation’s political sea-change won’t wash Alzheimer’s disease research funding offtrack, two legislators vowed at a Washington briefing.
Rather than descend into partisan budget-bickering under the new administration, lawmakers should reach across the aisle and pass funding bills to vigorously propel the nation toward its goal of having an effective disease-modifying Alzheimer’s disease therapy by 2025.
“If we make this a high-enough priority, we can meet that goal,” Rep. Paul Tonko (D-NY) said at a briefing sponsored by The Hill newspaper, with support by Eli Lilly. “We should prioritize the work we need to do to achieve it in both the House and Senate, and move forward both aggressively and progressively.”
“I am a strong proponent of investing in research. We simply must continue to put research dollars into Alzheimer’s. If we don’t invest, try to find a cure or treatment, Alzheimer’s will become the single largest driver of health care costs on both a federal and state level. We have to recognize this: We could, potentially, not even be able to provide care for all patients we will have, unless we find a treatment or a cure.”
After a decade of struggle, federal dollars for Alzheimer’s research have begun to creep up. Last year, Congress passed a historic $350 million increase in Alzheimer’s research funding at the National Institutes of Health, raising the total spending to $991 million for fiscal year 2016. Then, in June, the Senate Appropriations Committee approved a landmark $400 million funding increase. In July, the House Appropriations Committee approved its own $350 million bump.
In August, the NIH recommended a $414 million increase for fiscal year 2018. If both the fiscal year 2017 increase and fiscal year 2018 request are ultimately passed, funding levels would be very close to the $2 billion/year federal commitment that researchers and Alzheimer’s policy mavens say is necessary to achieve the 2025 goal, set forth in the National Plan to Address Alzheimer’s Disease.
“There’s no such thing as too much research funding,” Sen. Tillis said during the briefing. But, he added, that federal generosity must be wisely husbanded.
“There must also be a sense of discipline along with the funding. Money like that should be targeted in terms of which diseases we go after – they should be areas that have the broadest impact. In a world of scarce resources, we can’t afford to simply throw money around.”
Alzheimer’s research is a perfect example of this careful resource management, he said. The NIH has prepared its second “bypass budget,” a funding proposal that passes the normal legislative channels and goes directly to the President.
Based on the consensus of scientists involved in search for a disease-modifying therapy, this budget proposal estimates the additional money needed to meet the 2025 goal, above the NIH’s baseline Alzheimer’s funding.
Only two other areas of medicine have such a budget: cancer and HIV-AIDS, said Robert J. Egge, chief public policy officer of the Alzheimer’s Association.
“This budget goes right from the scientists to Congress with no filter by the Office of Management and Budget, and lands directly on the President’s desk,” he said in an interview. “It tells legislators what scientists need in order to accomplish that 2025 goal.”
The $2 billion/year figure, Mr. Egge noted, is a ground-floor suggestion. “That’s what we need right now to stay on track. We think the best way to figure out where we need to be in the long-term is to let the scientists at NIH tell us what they need, and we need Congress and the Administration to follow this year to year.”
Like Sen. Tillis and Rep. Tonko, Mr. Egge was upbeat in anticipating steady funding progress.
“The champions of Alzheimer’s funding who have made such a difference for us are all back and in their same positions,” with unstinting commitment to the cause.
Those legislators include:
• Rep. Tom Cole (R-OK), chairman of the House Appropriations Committee’s Subcommittee on Labor, Health and Human Services, Education and Related Agencies, which funds the NIH. In 2015, Rep. Cole shepherded through a $300 million appropriation for Alzheimer’s research, and the pending $350 million appropriation for fiscal year 2017.
• Sen. Roy Blunt (R-MO), who, as chairman of the Senate Appropriations Committee’s Subcommittee on Labor, Health and Human Services, Education and Related Agencies, secured June’s $400 million and a $350 million bump in 2015.
• Ranking member Sen. Patty Murray (D-WA), who cosponsored the Alzheimer’s Breakthrough Act of 2009, and who worked with Sen. Blunt to secure the recent Alzheimer’s funding increases.
Mr. Egge is not overly troubled about the antiscience rhetoric bandied about by some potential members of President-elect Trump’s administration. He predicted those rumblings will settle down and not negatively affect Alzheimer’s funding.
“I think all the talk of not believing in the science of biomedical research was premature,” he said. “I think it’s completely appropriate to say ‘We are going to watch closely and form opinions,’ but I have never been overly alarmed by this. As an Alzheimer’s advocate for strong science, I am waiting to see what the next steps are. President-elect Trump has said on the campaign trail that Alzheimer’s would be a top priority. Our champions from both parties are fully committed to this fight and recognize that science is the fundamental path to do so. I share this optimism. It’s not complacent optimism – it’s vigilant optimism that we will continue with the momentum we need to finally, squarely and effectively, address this disease.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – The nation’s political sea-change won’t wash Alzheimer’s disease research funding offtrack, two legislators vowed at a Washington briefing.
Rather than descend into partisan budget-bickering under the new administration, lawmakers should reach across the aisle and pass funding bills to vigorously propel the nation toward its goal of having an effective disease-modifying Alzheimer’s disease therapy by 2025.
“If we make this a high-enough priority, we can meet that goal,” Rep. Paul Tonko (D-NY) said at a briefing sponsored by The Hill newspaper, with support by Eli Lilly. “We should prioritize the work we need to do to achieve it in both the House and Senate, and move forward both aggressively and progressively.”
“I am a strong proponent of investing in research. We simply must continue to put research dollars into Alzheimer’s. If we don’t invest, try to find a cure or treatment, Alzheimer’s will become the single largest driver of health care costs on both a federal and state level. We have to recognize this: We could, potentially, not even be able to provide care for all patients we will have, unless we find a treatment or a cure.”
After a decade of struggle, federal dollars for Alzheimer’s research have begun to creep up. Last year, Congress passed a historic $350 million increase in Alzheimer’s research funding at the National Institutes of Health, raising the total spending to $991 million for fiscal year 2016. Then, in June, the Senate Appropriations Committee approved a landmark $400 million funding increase. In July, the House Appropriations Committee approved its own $350 million bump.
In August, the NIH recommended a $414 million increase for fiscal year 2018. If both the fiscal year 2017 increase and fiscal year 2018 request are ultimately passed, funding levels would be very close to the $2 billion/year federal commitment that researchers and Alzheimer’s policy mavens say is necessary to achieve the 2025 goal, set forth in the National Plan to Address Alzheimer’s Disease.
“There’s no such thing as too much research funding,” Sen. Tillis said during the briefing. But, he added, that federal generosity must be wisely husbanded.
“There must also be a sense of discipline along with the funding. Money like that should be targeted in terms of which diseases we go after – they should be areas that have the broadest impact. In a world of scarce resources, we can’t afford to simply throw money around.”
Alzheimer’s research is a perfect example of this careful resource management, he said. The NIH has prepared its second “bypass budget,” a funding proposal that passes the normal legislative channels and goes directly to the President.
Based on the consensus of scientists involved in search for a disease-modifying therapy, this budget proposal estimates the additional money needed to meet the 2025 goal, above the NIH’s baseline Alzheimer’s funding.
Only two other areas of medicine have such a budget: cancer and HIV-AIDS, said Robert J. Egge, chief public policy officer of the Alzheimer’s Association.
“This budget goes right from the scientists to Congress with no filter by the Office of Management and Budget, and lands directly on the President’s desk,” he said in an interview. “It tells legislators what scientists need in order to accomplish that 2025 goal.”
The $2 billion/year figure, Mr. Egge noted, is a ground-floor suggestion. “That’s what we need right now to stay on track. We think the best way to figure out where we need to be in the long-term is to let the scientists at NIH tell us what they need, and we need Congress and the Administration to follow this year to year.”
Like Sen. Tillis and Rep. Tonko, Mr. Egge was upbeat in anticipating steady funding progress.
“The champions of Alzheimer’s funding who have made such a difference for us are all back and in their same positions,” with unstinting commitment to the cause.
Those legislators include:
• Rep. Tom Cole (R-OK), chairman of the House Appropriations Committee’s Subcommittee on Labor, Health and Human Services, Education and Related Agencies, which funds the NIH. In 2015, Rep. Cole shepherded through a $300 million appropriation for Alzheimer’s research, and the pending $350 million appropriation for fiscal year 2017.
• Sen. Roy Blunt (R-MO), who, as chairman of the Senate Appropriations Committee’s Subcommittee on Labor, Health and Human Services, Education and Related Agencies, secured June’s $400 million and a $350 million bump in 2015.
• Ranking member Sen. Patty Murray (D-WA), who cosponsored the Alzheimer’s Breakthrough Act of 2009, and who worked with Sen. Blunt to secure the recent Alzheimer’s funding increases.
Mr. Egge is not overly troubled about the antiscience rhetoric bandied about by some potential members of President-elect Trump’s administration. He predicted those rumblings will settle down and not negatively affect Alzheimer’s funding.
“I think all the talk of not believing in the science of biomedical research was premature,” he said. “I think it’s completely appropriate to say ‘We are going to watch closely and form opinions,’ but I have never been overly alarmed by this. As an Alzheimer’s advocate for strong science, I am waiting to see what the next steps are. President-elect Trump has said on the campaign trail that Alzheimer’s would be a top priority. Our champions from both parties are fully committed to this fight and recognize that science is the fundamental path to do so. I share this optimism. It’s not complacent optimism – it’s vigilant optimism that we will continue with the momentum we need to finally, squarely and effectively, address this disease.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – The nation’s political sea-change won’t wash Alzheimer’s disease research funding offtrack, two legislators vowed at a Washington briefing.
Rather than descend into partisan budget-bickering under the new administration, lawmakers should reach across the aisle and pass funding bills to vigorously propel the nation toward its goal of having an effective disease-modifying Alzheimer’s disease therapy by 2025.
“If we make this a high-enough priority, we can meet that goal,” Rep. Paul Tonko (D-NY) said at a briefing sponsored by The Hill newspaper, with support by Eli Lilly. “We should prioritize the work we need to do to achieve it in both the House and Senate, and move forward both aggressively and progressively.”
“I am a strong proponent of investing in research. We simply must continue to put research dollars into Alzheimer’s. If we don’t invest, try to find a cure or treatment, Alzheimer’s will become the single largest driver of health care costs on both a federal and state level. We have to recognize this: We could, potentially, not even be able to provide care for all patients we will have, unless we find a treatment or a cure.”
After a decade of struggle, federal dollars for Alzheimer’s research have begun to creep up. Last year, Congress passed a historic $350 million increase in Alzheimer’s research funding at the National Institutes of Health, raising the total spending to $991 million for fiscal year 2016. Then, in June, the Senate Appropriations Committee approved a landmark $400 million funding increase. In July, the House Appropriations Committee approved its own $350 million bump.
In August, the NIH recommended a $414 million increase for fiscal year 2018. If both the fiscal year 2017 increase and fiscal year 2018 request are ultimately passed, funding levels would be very close to the $2 billion/year federal commitment that researchers and Alzheimer’s policy mavens say is necessary to achieve the 2025 goal, set forth in the National Plan to Address Alzheimer’s Disease.
“There’s no such thing as too much research funding,” Sen. Tillis said during the briefing. But, he added, that federal generosity must be wisely husbanded.
“There must also be a sense of discipline along with the funding. Money like that should be targeted in terms of which diseases we go after – they should be areas that have the broadest impact. In a world of scarce resources, we can’t afford to simply throw money around.”
Alzheimer’s research is a perfect example of this careful resource management, he said. The NIH has prepared its second “bypass budget,” a funding proposal that passes the normal legislative channels and goes directly to the President.
Based on the consensus of scientists involved in search for a disease-modifying therapy, this budget proposal estimates the additional money needed to meet the 2025 goal, above the NIH’s baseline Alzheimer’s funding.
Only two other areas of medicine have such a budget: cancer and HIV-AIDS, said Robert J. Egge, chief public policy officer of the Alzheimer’s Association.
“This budget goes right from the scientists to Congress with no filter by the Office of Management and Budget, and lands directly on the President’s desk,” he said in an interview. “It tells legislators what scientists need in order to accomplish that 2025 goal.”
The $2 billion/year figure, Mr. Egge noted, is a ground-floor suggestion. “That’s what we need right now to stay on track. We think the best way to figure out where we need to be in the long-term is to let the scientists at NIH tell us what they need, and we need Congress and the Administration to follow this year to year.”
Like Sen. Tillis and Rep. Tonko, Mr. Egge was upbeat in anticipating steady funding progress.
“The champions of Alzheimer’s funding who have made such a difference for us are all back and in their same positions,” with unstinting commitment to the cause.
Those legislators include:
• Rep. Tom Cole (R-OK), chairman of the House Appropriations Committee’s Subcommittee on Labor, Health and Human Services, Education and Related Agencies, which funds the NIH. In 2015, Rep. Cole shepherded through a $300 million appropriation for Alzheimer’s research, and the pending $350 million appropriation for fiscal year 2017.
• Sen. Roy Blunt (R-MO), who, as chairman of the Senate Appropriations Committee’s Subcommittee on Labor, Health and Human Services, Education and Related Agencies, secured June’s $400 million and a $350 million bump in 2015.
• Ranking member Sen. Patty Murray (D-WA), who cosponsored the Alzheimer’s Breakthrough Act of 2009, and who worked with Sen. Blunt to secure the recent Alzheimer’s funding increases.
Mr. Egge is not overly troubled about the antiscience rhetoric bandied about by some potential members of President-elect Trump’s administration. He predicted those rumblings will settle down and not negatively affect Alzheimer’s funding.
“I think all the talk of not believing in the science of biomedical research was premature,” he said. “I think it’s completely appropriate to say ‘We are going to watch closely and form opinions,’ but I have never been overly alarmed by this. As an Alzheimer’s advocate for strong science, I am waiting to see what the next steps are. President-elect Trump has said on the campaign trail that Alzheimer’s would be a top priority. Our champions from both parties are fully committed to this fight and recognize that science is the fundamental path to do so. I share this optimism. It’s not complacent optimism – it’s vigilant optimism that we will continue with the momentum we need to finally, squarely and effectively, address this disease.”
msullivan@frontlinemedcom.com
On Twitter @alz_gal
Mycophenolate puts lupus patients in remission faster than azathioprine
WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD, reported at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint of the trial was complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD, reported at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint of the trial was complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD, reported at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint of the trial was complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
Key clinical point:
Major finding: Complete remission rates at 3 months were 32% for mycophenolate and 19% for azathioprine.
Data source: A 24-month, open-label, randomized trial of 240 patients.
Disclosures: The Spanish Ministry of Health funded the study. Dr. Cortés-Hernández had no relevant financial disclosures.
Early-onset preeclampsia more likely to occur in women with lupus
WASHINGTON – Women with systemic lupus erythematosus are nine times more likely to develop early-onset preeclampsia during a first pregnancy than are women without the disease, according a study of two Swedish national population-based registries.
The risk of preeclampsia occurring before 34 weeks’ gestation declined with subsequent pregnancies, but it remained significantly elevated above the background risk, Julia F. Simard, ScD, said at the annual meeting of the American College of Rheumatology.
During the study period, 742 births to women with SLE were matched with 10,484 births to women without the disease. The mean age of the patients was 31 years.
Of the women with SLE, 5% had pregestational hypertension and 3% had pregestational diabetes. Antiphospholipid antibodies were present in 2%. Among the controls, less than 1% had pregestational hypertension, and 1.3% had pregestational diabetes. There were no healthy controls with antiphospholipid antibodies.
In the entire cohort, there were 438 cases of preeclampsia: 82 in the SLE group and 356 in the control group. In the fully adjusted model, this translated to nearly a tripling of relative risk (RR, 2.7).
Preeclampsia more commonly occurred in first births, based on 56 cases in the SLE group and 225 in the control group. SLE patients in their first pregnancy also had a tripling of risk (RR, 3.2). Among subsequent births, there were 157 cases: 26 in the SLE group and 131 in the control group. The relative risk for preeclampsia was lower, but still significantly elevated (RR, 2).
There were 87 cases of early-onset preeclampsia: 32 in the SLE group and 55 in the control group. Women with SLE were more than six times more likely to develop the disorder (RR, 6.3). Early-onset preeclampsia was more common in first births for both groups: 24 in the SLE group and 34 in the control group, for a ninefold increased risk (RR, 9.3).
Again, the incidence decreased with subsequent births in both groups: 8 cases in the SLE group and 21 in the control group. But SLE patients still faced a significant threefold increase in risk (RR, 2.8).
“Antiphospholipid antibodies appear to be an important risk factor that needs to more fully understood,” Dr. Simard said. “But the risk seems to be independent of other traditional risk factors, like pregestational hypertension, body mass index, and smoking.”
She and her associates had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Women with systemic lupus erythematosus are nine times more likely to develop early-onset preeclampsia during a first pregnancy than are women without the disease, according a study of two Swedish national population-based registries.
The risk of preeclampsia occurring before 34 weeks’ gestation declined with subsequent pregnancies, but it remained significantly elevated above the background risk, Julia F. Simard, ScD, said at the annual meeting of the American College of Rheumatology.
During the study period, 742 births to women with SLE were matched with 10,484 births to women without the disease. The mean age of the patients was 31 years.
Of the women with SLE, 5% had pregestational hypertension and 3% had pregestational diabetes. Antiphospholipid antibodies were present in 2%. Among the controls, less than 1% had pregestational hypertension, and 1.3% had pregestational diabetes. There were no healthy controls with antiphospholipid antibodies.
In the entire cohort, there were 438 cases of preeclampsia: 82 in the SLE group and 356 in the control group. In the fully adjusted model, this translated to nearly a tripling of relative risk (RR, 2.7).
Preeclampsia more commonly occurred in first births, based on 56 cases in the SLE group and 225 in the control group. SLE patients in their first pregnancy also had a tripling of risk (RR, 3.2). Among subsequent births, there were 157 cases: 26 in the SLE group and 131 in the control group. The relative risk for preeclampsia was lower, but still significantly elevated (RR, 2).
There were 87 cases of early-onset preeclampsia: 32 in the SLE group and 55 in the control group. Women with SLE were more than six times more likely to develop the disorder (RR, 6.3). Early-onset preeclampsia was more common in first births for both groups: 24 in the SLE group and 34 in the control group, for a ninefold increased risk (RR, 9.3).
Again, the incidence decreased with subsequent births in both groups: 8 cases in the SLE group and 21 in the control group. But SLE patients still faced a significant threefold increase in risk (RR, 2.8).
“Antiphospholipid antibodies appear to be an important risk factor that needs to more fully understood,” Dr. Simard said. “But the risk seems to be independent of other traditional risk factors, like pregestational hypertension, body mass index, and smoking.”
She and her associates had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Women with systemic lupus erythematosus are nine times more likely to develop early-onset preeclampsia during a first pregnancy than are women without the disease, according a study of two Swedish national population-based registries.
The risk of preeclampsia occurring before 34 weeks’ gestation declined with subsequent pregnancies, but it remained significantly elevated above the background risk, Julia F. Simard, ScD, said at the annual meeting of the American College of Rheumatology.
During the study period, 742 births to women with SLE were matched with 10,484 births to women without the disease. The mean age of the patients was 31 years.
Of the women with SLE, 5% had pregestational hypertension and 3% had pregestational diabetes. Antiphospholipid antibodies were present in 2%. Among the controls, less than 1% had pregestational hypertension, and 1.3% had pregestational diabetes. There were no healthy controls with antiphospholipid antibodies.
In the entire cohort, there were 438 cases of preeclampsia: 82 in the SLE group and 356 in the control group. In the fully adjusted model, this translated to nearly a tripling of relative risk (RR, 2.7).
Preeclampsia more commonly occurred in first births, based on 56 cases in the SLE group and 225 in the control group. SLE patients in their first pregnancy also had a tripling of risk (RR, 3.2). Among subsequent births, there were 157 cases: 26 in the SLE group and 131 in the control group. The relative risk for preeclampsia was lower, but still significantly elevated (RR, 2).
There were 87 cases of early-onset preeclampsia: 32 in the SLE group and 55 in the control group. Women with SLE were more than six times more likely to develop the disorder (RR, 6.3). Early-onset preeclampsia was more common in first births for both groups: 24 in the SLE group and 34 in the control group, for a ninefold increased risk (RR, 9.3).
Again, the incidence decreased with subsequent births in both groups: 8 cases in the SLE group and 21 in the control group. But SLE patients still faced a significant threefold increase in risk (RR, 2.8).
“Antiphospholipid antibodies appear to be an important risk factor that needs to more fully understood,” Dr. Simard said. “But the risk seems to be independent of other traditional risk factors, like pregestational hypertension, body mass index, and smoking.”
She and her associates had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
ACR ANNUAL MEETING
Key clinical point:
Major finding: Women with SLE in a first pregnancy had a ninefold greater risk of early-onset preeclampsia than did healthy control patients in their first pregnancy.
Data source: The data were extracted from two Swedish national population-based registries.
Disclosures: Dr, Simard and her associates had no financial disclosures.
VIDEO: Denosumab trumps risedronate in bone building for glucocorticoid-induced osteoporosis
WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.
Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.
“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.
Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.
The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.
The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.
In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.
The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.
Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.
Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.
Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.
“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.
Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.
The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.
The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.
In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.
The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.
Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.
Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.
Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.
“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.
Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.
The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.
The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.
In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.
The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.
Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.
Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: In patients on continuous glucocorticoid therapy, denosumab increased BMD by 4.4% at the lumbar spine and 2.1% at the total hip, compared with increases of 2.3% and 0.6% with risedronate.
Data source: 12-month results of the 24-month, phase III study of 795 patients.
Disclosures: Amgen sponsored the study. Dr. Saag has been a consultant for the company. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.
Open, laparoscopic, robotic approaches all sound for distal pancreatectomy
WASHINGTON – The three approaches to distal pancreatectomy – open, laparoscopic, and robotic – are equally safe and oncologically sound methods in properly selected patients, findings from a NSQIP database study show.
“The three approaches have specific indications for use and advantages in well-selected patients; therefore, demonstrating the superiority of one technique over another remains challenging,” said Dimitrios Xourafas, MD, in his presentation at the annual clinical congress of the American College of Surgeons.
Laparoscopic surgeries are more likely to result in open conversions than are robotic surgeries – but robotic surgeries take more time to complete. Open surgeries may be best for advanced disease. But all in all, there are no overriding advantages or disadvantages to any of them, reported Dr. Xourafas, a research fellow in surgery at Brigham and Women’s Hospital, Boston.
He and his colleagues used the American College of Surgeons National Surgical Quality Improvement (NSQIP) database for detailed information on 1,815 distal pancreatectomies performed in 2014. These they separated into three groups: open (921), laparoscopic (694) and robotic (200).
There were no differences in baseline characteristics. Mean age of the patients was 62 years. More than 70% of each group had serious comorbidities. Significantly more in the open surgery group had lost 10% or more of their body weight since diagnosis; this was probably related to a higher rate of preoperative chemotherapy in this group, Dr. Xourafas said. Patients having open surgery also were more likely to have undergone radiation therapy.
There were significant, but mixed, differences in operative outcomes. Surgery was longest in the robotic group (243 minutes vs. 205 minutes in the laparoscopic group and 222 minutes in the open group.) Laparoscopic procedures were more likely to convert to open than were robotic (16% vs. 8%). Blood loss was significantly greater in the open group, with 21% needing transfusion vs. 5% laparoscopic and 6% robotic. Close to 100% of patients in the robotic and open groups needed no vascular resection and no reconstruction. In the open group, fewer patients (88%) had no vascular resection, and 84% required no reconstruction, suggesting that these cases were more advanced disease. This finding was also borne out by the larger percentage of tumors that staged at T3 or higher (34% in the open group vs. about 20% in the other groups). However, about half of each group had a malignant tumor subtype and lesion sizes were similar.
Surgical site infections were more common in the open group (10% vs. 7% of the other groups). The length of stay was longest in the open group (7 days vs. 5 in the other groups). The robotic group had the highest rate of pancreatic fistula (21%) although this was not significantly different from the open and laparoscopic rates (16% and 17%, respectively).
Overall morbidity was 45% in the open group, 36% in the laparoscopic group, and 37% in the robotic group. Mortality was 1.5% in the open group, 1% in the laparoscopic group, and 0.5% in the robotic group – not significantly different.
Dr. Xourafas had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
WASHINGTON – The three approaches to distal pancreatectomy – open, laparoscopic, and robotic – are equally safe and oncologically sound methods in properly selected patients, findings from a NSQIP database study show.
“The three approaches have specific indications for use and advantages in well-selected patients; therefore, demonstrating the superiority of one technique over another remains challenging,” said Dimitrios Xourafas, MD, in his presentation at the annual clinical congress of the American College of Surgeons.
Laparoscopic surgeries are more likely to result in open conversions than are robotic surgeries – but robotic surgeries take more time to complete. Open surgeries may be best for advanced disease. But all in all, there are no overriding advantages or disadvantages to any of them, reported Dr. Xourafas, a research fellow in surgery at Brigham and Women’s Hospital, Boston.
He and his colleagues used the American College of Surgeons National Surgical Quality Improvement (NSQIP) database for detailed information on 1,815 distal pancreatectomies performed in 2014. These they separated into three groups: open (921), laparoscopic (694) and robotic (200).
There were no differences in baseline characteristics. Mean age of the patients was 62 years. More than 70% of each group had serious comorbidities. Significantly more in the open surgery group had lost 10% or more of their body weight since diagnosis; this was probably related to a higher rate of preoperative chemotherapy in this group, Dr. Xourafas said. Patients having open surgery also were more likely to have undergone radiation therapy.
There were significant, but mixed, differences in operative outcomes. Surgery was longest in the robotic group (243 minutes vs. 205 minutes in the laparoscopic group and 222 minutes in the open group.) Laparoscopic procedures were more likely to convert to open than were robotic (16% vs. 8%). Blood loss was significantly greater in the open group, with 21% needing transfusion vs. 5% laparoscopic and 6% robotic. Close to 100% of patients in the robotic and open groups needed no vascular resection and no reconstruction. In the open group, fewer patients (88%) had no vascular resection, and 84% required no reconstruction, suggesting that these cases were more advanced disease. This finding was also borne out by the larger percentage of tumors that staged at T3 or higher (34% in the open group vs. about 20% in the other groups). However, about half of each group had a malignant tumor subtype and lesion sizes were similar.
Surgical site infections were more common in the open group (10% vs. 7% of the other groups). The length of stay was longest in the open group (7 days vs. 5 in the other groups). The robotic group had the highest rate of pancreatic fistula (21%) although this was not significantly different from the open and laparoscopic rates (16% and 17%, respectively).
Overall morbidity was 45% in the open group, 36% in the laparoscopic group, and 37% in the robotic group. Mortality was 1.5% in the open group, 1% in the laparoscopic group, and 0.5% in the robotic group – not significantly different.
Dr. Xourafas had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
WASHINGTON – The three approaches to distal pancreatectomy – open, laparoscopic, and robotic – are equally safe and oncologically sound methods in properly selected patients, findings from a NSQIP database study show.
“The three approaches have specific indications for use and advantages in well-selected patients; therefore, demonstrating the superiority of one technique over another remains challenging,” said Dimitrios Xourafas, MD, in his presentation at the annual clinical congress of the American College of Surgeons.
Laparoscopic surgeries are more likely to result in open conversions than are robotic surgeries – but robotic surgeries take more time to complete. Open surgeries may be best for advanced disease. But all in all, there are no overriding advantages or disadvantages to any of them, reported Dr. Xourafas, a research fellow in surgery at Brigham and Women’s Hospital, Boston.
He and his colleagues used the American College of Surgeons National Surgical Quality Improvement (NSQIP) database for detailed information on 1,815 distal pancreatectomies performed in 2014. These they separated into three groups: open (921), laparoscopic (694) and robotic (200).
There were no differences in baseline characteristics. Mean age of the patients was 62 years. More than 70% of each group had serious comorbidities. Significantly more in the open surgery group had lost 10% or more of their body weight since diagnosis; this was probably related to a higher rate of preoperative chemotherapy in this group, Dr. Xourafas said. Patients having open surgery also were more likely to have undergone radiation therapy.
There were significant, but mixed, differences in operative outcomes. Surgery was longest in the robotic group (243 minutes vs. 205 minutes in the laparoscopic group and 222 minutes in the open group.) Laparoscopic procedures were more likely to convert to open than were robotic (16% vs. 8%). Blood loss was significantly greater in the open group, with 21% needing transfusion vs. 5% laparoscopic and 6% robotic. Close to 100% of patients in the robotic and open groups needed no vascular resection and no reconstruction. In the open group, fewer patients (88%) had no vascular resection, and 84% required no reconstruction, suggesting that these cases were more advanced disease. This finding was also borne out by the larger percentage of tumors that staged at T3 or higher (34% in the open group vs. about 20% in the other groups). However, about half of each group had a malignant tumor subtype and lesion sizes were similar.
Surgical site infections were more common in the open group (10% vs. 7% of the other groups). The length of stay was longest in the open group (7 days vs. 5 in the other groups). The robotic group had the highest rate of pancreatic fistula (21%) although this was not significantly different from the open and laparoscopic rates (16% and 17%, respectively).
Overall morbidity was 45% in the open group, 36% in the laparoscopic group, and 37% in the robotic group. Mortality was 1.5% in the open group, 1% in the laparoscopic group, and 0.5% in the robotic group – not significantly different.
Dr. Xourafas had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
AT THE ACS CLINICAL CONGRESS
Key clinical point:
Major finding: Surgery was longest in the robotic group (243 minutes), but more patients in the open group needed transfusions (21% vs. 5% of the other groups).
Data source: The database review comprised 1,815 patients.
Disclosures: Dr. Xourafas had no financial disclosures.