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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
One-time AMH level predicts rapid perimenopausal bone loss
BOSTON – Anti-Müllerian hormone levels strongly predict the rate of perimenopausal loss of bone mineral density and might help identify women who need early intervention to prevent future osteoporotic fractures, according to data from a review of 474 perimenopausal women that was presented at the annual meeting of the Endocrine Society.
The team matched anti-Müllerian hormone (AMH) levels and bone mineral density (BMD) measurements taken 2-4 years before the final menstrual period to BMD measurements taken 3 years later. The women were part of the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter study of women during their middle years.
When perimenopausal AMH “goes below 250 pg/mL, you are beginning to lose bone, and, when it goes below 200 pg/mL, you are losing bone fast, so that’s when you might want to intervene.” The finding “opens up the possibility of identifying women who are going to lose the most bone mass during the transition and targeting them before they have lost a substantial amount,” said lead investigator Dr. Arun Karlamangla of the department of geriatrics at the University of California, Los Angeles.
BMD loss is normal during menopause but rates of decline vary among women. AMH is a product of ovarian granulosa cells commonly used in fertility clinics to gauge ovarian reserve, but AMH levels also decline during menopause, and in a fairly stable fashion, he explained.
The women in SWAN were 42-52 years old at baseline with an intact uterus, at least one ovary, and no use of exogenous hormones. Blood was drawn during the early follicular phase of the menstrual cycle.
The median rate of BMD decline was 1.26% per year in the lumbar spine and 1.03% per year in the femoral neck. The median AMH was 49 pg/mL but varied widely.
Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in spine BMD and 0.13% per year faster decline in femoral neck BMD. Each fourfold decrement was also associated with an 18% increase in the odds of faster than median decline in spine BMD and 17% increase in the odds of faster than median decline in femoral neck BMD. The fast losers lost more than 2% of their BMD per year in both the lumbar spine and femoral neck.
The results were the same after adjustment for follicle-stimulating hormone and estrogen levels, “so AMH provides information that cannot be obtained from estrogen and FSH,” Dr. Karlamangla said.
He cautioned that the technique needs further development and validation before it’s ready for the clinic. The team used the PicoAMH test from Ansh Labs in Webster, Tex.
The investigators had no disclosures. Ansh provided the assays for free. SWAN is funded by the National Institutes of Health.
The current recommendation is to start bone mineral density screening in women at age 65 years. All of us who see patients in the menopause years worry that we are missing someone with faster than normal bone loss. Fast losers are critical to identify because if we wait until they are 65 years old, it’s too late. A clinical test such as this to identify fast losers for earlier BMD measurement would be a tremendous benefit.
Dr. Cynthia Stuenkel is a clinical professor of endocrinology at the University of California, San Diego. She moderated the presentation and was not involved in the research.
The current recommendation is to start bone mineral density screening in women at age 65 years. All of us who see patients in the menopause years worry that we are missing someone with faster than normal bone loss. Fast losers are critical to identify because if we wait until they are 65 years old, it’s too late. A clinical test such as this to identify fast losers for earlier BMD measurement would be a tremendous benefit.
Dr. Cynthia Stuenkel is a clinical professor of endocrinology at the University of California, San Diego. She moderated the presentation and was not involved in the research.
The current recommendation is to start bone mineral density screening in women at age 65 years. All of us who see patients in the menopause years worry that we are missing someone with faster than normal bone loss. Fast losers are critical to identify because if we wait until they are 65 years old, it’s too late. A clinical test such as this to identify fast losers for earlier BMD measurement would be a tremendous benefit.
Dr. Cynthia Stuenkel is a clinical professor of endocrinology at the University of California, San Diego. She moderated the presentation and was not involved in the research.
BOSTON – Anti-Müllerian hormone levels strongly predict the rate of perimenopausal loss of bone mineral density and might help identify women who need early intervention to prevent future osteoporotic fractures, according to data from a review of 474 perimenopausal women that was presented at the annual meeting of the Endocrine Society.
The team matched anti-Müllerian hormone (AMH) levels and bone mineral density (BMD) measurements taken 2-4 years before the final menstrual period to BMD measurements taken 3 years later. The women were part of the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter study of women during their middle years.
When perimenopausal AMH “goes below 250 pg/mL, you are beginning to lose bone, and, when it goes below 200 pg/mL, you are losing bone fast, so that’s when you might want to intervene.” The finding “opens up the possibility of identifying women who are going to lose the most bone mass during the transition and targeting them before they have lost a substantial amount,” said lead investigator Dr. Arun Karlamangla of the department of geriatrics at the University of California, Los Angeles.
BMD loss is normal during menopause but rates of decline vary among women. AMH is a product of ovarian granulosa cells commonly used in fertility clinics to gauge ovarian reserve, but AMH levels also decline during menopause, and in a fairly stable fashion, he explained.
The women in SWAN were 42-52 years old at baseline with an intact uterus, at least one ovary, and no use of exogenous hormones. Blood was drawn during the early follicular phase of the menstrual cycle.
The median rate of BMD decline was 1.26% per year in the lumbar spine and 1.03% per year in the femoral neck. The median AMH was 49 pg/mL but varied widely.
Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in spine BMD and 0.13% per year faster decline in femoral neck BMD. Each fourfold decrement was also associated with an 18% increase in the odds of faster than median decline in spine BMD and 17% increase in the odds of faster than median decline in femoral neck BMD. The fast losers lost more than 2% of their BMD per year in both the lumbar spine and femoral neck.
The results were the same after adjustment for follicle-stimulating hormone and estrogen levels, “so AMH provides information that cannot be obtained from estrogen and FSH,” Dr. Karlamangla said.
He cautioned that the technique needs further development and validation before it’s ready for the clinic. The team used the PicoAMH test from Ansh Labs in Webster, Tex.
The investigators had no disclosures. Ansh provided the assays for free. SWAN is funded by the National Institutes of Health.
BOSTON – Anti-Müllerian hormone levels strongly predict the rate of perimenopausal loss of bone mineral density and might help identify women who need early intervention to prevent future osteoporotic fractures, according to data from a review of 474 perimenopausal women that was presented at the annual meeting of the Endocrine Society.
The team matched anti-Müllerian hormone (AMH) levels and bone mineral density (BMD) measurements taken 2-4 years before the final menstrual period to BMD measurements taken 3 years later. The women were part of the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter study of women during their middle years.
When perimenopausal AMH “goes below 250 pg/mL, you are beginning to lose bone, and, when it goes below 200 pg/mL, you are losing bone fast, so that’s when you might want to intervene.” The finding “opens up the possibility of identifying women who are going to lose the most bone mass during the transition and targeting them before they have lost a substantial amount,” said lead investigator Dr. Arun Karlamangla of the department of geriatrics at the University of California, Los Angeles.
BMD loss is normal during menopause but rates of decline vary among women. AMH is a product of ovarian granulosa cells commonly used in fertility clinics to gauge ovarian reserve, but AMH levels also decline during menopause, and in a fairly stable fashion, he explained.
The women in SWAN were 42-52 years old at baseline with an intact uterus, at least one ovary, and no use of exogenous hormones. Blood was drawn during the early follicular phase of the menstrual cycle.
The median rate of BMD decline was 1.26% per year in the lumbar spine and 1.03% per year in the femoral neck. The median AMH was 49 pg/mL but varied widely.
Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in spine BMD and 0.13% per year faster decline in femoral neck BMD. Each fourfold decrement was also associated with an 18% increase in the odds of faster than median decline in spine BMD and 17% increase in the odds of faster than median decline in femoral neck BMD. The fast losers lost more than 2% of their BMD per year in both the lumbar spine and femoral neck.
The results were the same after adjustment for follicle-stimulating hormone and estrogen levels, “so AMH provides information that cannot be obtained from estrogen and FSH,” Dr. Karlamangla said.
He cautioned that the technique needs further development and validation before it’s ready for the clinic. The team used the PicoAMH test from Ansh Labs in Webster, Tex.
The investigators had no disclosures. Ansh provided the assays for free. SWAN is funded by the National Institutes of Health.
AT ENDO 2016
Key clinical point: Anti-Müllerian hormone levels strongly predict the rate of perimenopausal bone mineral density loss and might help identify women who need early intervention to prevent future osteoporotic fractures, according to a review of 474 perimenopausal women that was presented at the Endocrine Society annual meeting.
Major finding: Adjusted for age, body mass index, smoking, race, and study site, the team found that for each 75% (or fourfold) decrement in AMH level, there was a 0.15% per year faster decline in lumbar spine BMD and 0.13% per year faster decline in femoral neck BMD.
Data source: Review of 474 perimenopausal women in the Study of Women’s Health Across the Nation.
Disclosures: The investigators had no disclosures. Ansh Labs provided the assays for free. SWAN is funded by the National Institutes of Health.
TSH antibody levels predict Graves relapse after thionamides
BOSTON – Eighty-six percent of Graves disease patients with TSH receptor antibody levels of at least 2.0 mU/L at the end of thionamide therapy will relapse within 4 years, according to a British review.
TSH receptor antibody (TRAb) levels “are useful not only as a diagnostic tool but also as a prognostic tool. In patients where the risks of recurrent thyrotoxicosis are unacceptably high” – the elderly and those at risk for cardiovascular disease – “strong consideration should be given to primary radioiodine therapy” instead of thionamides, said investigator Nyo Nyo Tun of the Edinburgh Centre for Endocrinology and Diabetes.
Previous studies have suggested age and other risk factors for relapse after thionamides, but “have not [definitively] shown if elevation of TRAb levels” are predictive, she said at the annual meeting of the Endocrine Society.
Primary therapy with thionamides is more common in Europe than in the United States, where radioiodine tends to be the first choice. Part of the problem is that recurrence is known to be high after thionamides. The study suggests that using TRAb can help weed out patients who are likely to fail so that thionamides can be used with greater long-term success. Ms. Tun said the Edinburgh center routinely uses TRAb to guide Graves treatment; patients with high levels either stay on thionamide for prolonged periods or opt for radioiodine.
The investigators retrospectively studied 266 patients with a first presentation of Graves disease who completed a course of thionamide at two U.K. hospitals. In addition to TRAb levels at diagnosis and cessation of thionamide, they assessed age, sex, smoking status, free T4 levels, total T3, and time to normalization of thyroid function over 4 years of follow-up.
After thionamide cessation, thyrotoxicosis recurred in 31% of patients (82/266) at 1 year, 43% (111/261) at 2 years, 54% (125/232) at 3 years, and 66% (128/193) at 4 years.
Very high TRAb levels at diagnosis – those above 12 mU/L – were associated with a statistically significant 84% risk of recurrence over a 4-year period, compared with a 57% risk with diagnosis levels below 5mU/L (P = .002).
TRAb levels below 0.9 mU/L at cessation of an 18-month course of thionamide treatment were associated with a 22% risk of recurrence at 1 year and a 58% risk at 4 years. Those risks were significantly higher in patients whose TRAb levels were at least 2 mU/L at thionamide cessation, who had a 51% risk at 1 year and an 86% risk at 4 years (P less than 0.001). Relapse risk was highest in the first 18 months after cessation.
Younger age and time to TSH normalization also predicted relapse to some extent. Among patients who stayed in remission for 4 years, TSH normalized at a median of about 4 months after the start of drug treatment, but 6 months in those who relapsed. Similarly, patients who relapsed were a median of 39 years old at diagnosis; those who did not were a median of 47.
The investigators had no relevant financial disclosures.
The measurement of antibodies to the thyroid-stimulating hormone receptor is a useful clinical test that should be much more widely used in the United States. It’s a very accurate predictor of who’s going to get recurrent Grave’s disease after antithyroid drugs, but it’s misunderstood and not trusted.
 |
Dr. Terry Davies |
When the test was first introduced, many major thyroid experts didn’t accept it and didn’t believe it was useful based on research at the time. The difference with the current study is that it was done carefully.
Dr. Terry Davies is the director of the division of endocrinology, diabetes, and bone diseases at the Mount Sinai Beth Israel Medical Center in New York. He moderated the presentation and was not involved in the work.
The measurement of antibodies to the thyroid-stimulating hormone receptor is a useful clinical test that should be much more widely used in the United States. It’s a very accurate predictor of who’s going to get recurrent Grave’s disease after antithyroid drugs, but it’s misunderstood and not trusted.
|
Dr. Terry Davies |
When the test was first introduced, many major thyroid experts didn’t accept it and didn’t believe it was useful based on research at the time. The difference with the current study is that it was done carefully.
Dr. Terry Davies is the director of the division of endocrinology, diabetes, and bone diseases at the Mount Sinai Beth Israel Medical Center in New York. He moderated the presentation and was not involved in the work.
The measurement of antibodies to the thyroid-stimulating hormone receptor is a useful clinical test that should be much more widely used in the United States. It’s a very accurate predictor of who’s going to get recurrent Grave’s disease after antithyroid drugs, but it’s misunderstood and not trusted.
|
Dr. Terry Davies |
When the test was first introduced, many major thyroid experts didn’t accept it and didn’t believe it was useful based on research at the time. The difference with the current study is that it was done carefully.
Dr. Terry Davies is the director of the division of endocrinology, diabetes, and bone diseases at the Mount Sinai Beth Israel Medical Center in New York. He moderated the presentation and was not involved in the work.
BOSTON – Eighty-six percent of Graves disease patients with TSH receptor antibody levels of at least 2.0 mU/L at the end of thionamide therapy will relapse within 4 years, according to a British review.
TSH receptor antibody (TRAb) levels “are useful not only as a diagnostic tool but also as a prognostic tool. In patients where the risks of recurrent thyrotoxicosis are unacceptably high” – the elderly and those at risk for cardiovascular disease – “strong consideration should be given to primary radioiodine therapy” instead of thionamides, said investigator Nyo Nyo Tun of the Edinburgh Centre for Endocrinology and Diabetes.
Previous studies have suggested age and other risk factors for relapse after thionamides, but “have not [definitively] shown if elevation of TRAb levels” are predictive, she said at the annual meeting of the Endocrine Society.
Primary therapy with thionamides is more common in Europe than in the United States, where radioiodine tends to be the first choice. Part of the problem is that recurrence is known to be high after thionamides. The study suggests that using TRAb can help weed out patients who are likely to fail so that thionamides can be used with greater long-term success. Ms. Tun said the Edinburgh center routinely uses TRAb to guide Graves treatment; patients with high levels either stay on thionamide for prolonged periods or opt for radioiodine.
The investigators retrospectively studied 266 patients with a first presentation of Graves disease who completed a course of thionamide at two U.K. hospitals. In addition to TRAb levels at diagnosis and cessation of thionamide, they assessed age, sex, smoking status, free T4 levels, total T3, and time to normalization of thyroid function over 4 years of follow-up.
After thionamide cessation, thyrotoxicosis recurred in 31% of patients (82/266) at 1 year, 43% (111/261) at 2 years, 54% (125/232) at 3 years, and 66% (128/193) at 4 years.
Very high TRAb levels at diagnosis – those above 12 mU/L – were associated with a statistically significant 84% risk of recurrence over a 4-year period, compared with a 57% risk with diagnosis levels below 5mU/L (P = .002).
TRAb levels below 0.9 mU/L at cessation of an 18-month course of thionamide treatment were associated with a 22% risk of recurrence at 1 year and a 58% risk at 4 years. Those risks were significantly higher in patients whose TRAb levels were at least 2 mU/L at thionamide cessation, who had a 51% risk at 1 year and an 86% risk at 4 years (P less than 0.001). Relapse risk was highest in the first 18 months after cessation.
Younger age and time to TSH normalization also predicted relapse to some extent. Among patients who stayed in remission for 4 years, TSH normalized at a median of about 4 months after the start of drug treatment, but 6 months in those who relapsed. Similarly, patients who relapsed were a median of 39 years old at diagnosis; those who did not were a median of 47.
The investigators had no relevant financial disclosures.
BOSTON – Eighty-six percent of Graves disease patients with TSH receptor antibody levels of at least 2.0 mU/L at the end of thionamide therapy will relapse within 4 years, according to a British review.
TSH receptor antibody (TRAb) levels “are useful not only as a diagnostic tool but also as a prognostic tool. In patients where the risks of recurrent thyrotoxicosis are unacceptably high” – the elderly and those at risk for cardiovascular disease – “strong consideration should be given to primary radioiodine therapy” instead of thionamides, said investigator Nyo Nyo Tun of the Edinburgh Centre for Endocrinology and Diabetes.
Previous studies have suggested age and other risk factors for relapse after thionamides, but “have not [definitively] shown if elevation of TRAb levels” are predictive, she said at the annual meeting of the Endocrine Society.
Primary therapy with thionamides is more common in Europe than in the United States, where radioiodine tends to be the first choice. Part of the problem is that recurrence is known to be high after thionamides. The study suggests that using TRAb can help weed out patients who are likely to fail so that thionamides can be used with greater long-term success. Ms. Tun said the Edinburgh center routinely uses TRAb to guide Graves treatment; patients with high levels either stay on thionamide for prolonged periods or opt for radioiodine.
The investigators retrospectively studied 266 patients with a first presentation of Graves disease who completed a course of thionamide at two U.K. hospitals. In addition to TRAb levels at diagnosis and cessation of thionamide, they assessed age, sex, smoking status, free T4 levels, total T3, and time to normalization of thyroid function over 4 years of follow-up.
After thionamide cessation, thyrotoxicosis recurred in 31% of patients (82/266) at 1 year, 43% (111/261) at 2 years, 54% (125/232) at 3 years, and 66% (128/193) at 4 years.
Very high TRAb levels at diagnosis – those above 12 mU/L – were associated with a statistically significant 84% risk of recurrence over a 4-year period, compared with a 57% risk with diagnosis levels below 5mU/L (P = .002).
TRAb levels below 0.9 mU/L at cessation of an 18-month course of thionamide treatment were associated with a 22% risk of recurrence at 1 year and a 58% risk at 4 years. Those risks were significantly higher in patients whose TRAb levels were at least 2 mU/L at thionamide cessation, who had a 51% risk at 1 year and an 86% risk at 4 years (P less than 0.001). Relapse risk was highest in the first 18 months after cessation.
Younger age and time to TSH normalization also predicted relapse to some extent. Among patients who stayed in remission for 4 years, TSH normalized at a median of about 4 months after the start of drug treatment, but 6 months in those who relapsed. Similarly, patients who relapsed were a median of 39 years old at diagnosis; those who did not were a median of 47.
The investigators had no relevant financial disclosures.
AT ENDO 2016
Key clinical point: Opt for radioiodine when Grave’s patients present with thyroid-stimulating hormone receptor antibody levels above 12 mU/L.
Major finding: Eighty-six percent of Grave’s disease patients with TSH receptor antibody levels of at least 2.0 mU/L at the end of thionamide therapy will relapse within 4 years.
Data source: A British review of 266 Grave’s patients treated with thionamides for 18 months.
Disclosures: The investigators had no relevant financial disclosures.
Fewer new lesions, side effects differentiate fingolimod from dimethyl fumarate
VANCOUVER – Multiple sclerosis patients discontinued treatment and relapsed earlier with dimethyl fumarate (Tecfidera) than with fingolimod (Gilenya), and had more gadolinium-enhancing lesions at 12 months, in a propensity score matching analysis involving 775 patients at the Cleveland Clinic.
“Based on these data, I now [favor] Gilenya over Tecfidera; Gilenya works a little bit better,” lead investigator and staff neurologist Carrie Hersh said at the annual meeting of the American Academy of Neurology.
The two drugs performed about equally in clinical trials, but Dr. Hersh and her colleagues said fingolimod seems to have the edge in clinical practice; they wanted to see if that hunch held up to scrutiny.
In the single-center cohort study, about 30% of the 458 dimethyl fumarate patients discontinued the drug after an average of 4 months, and about 14% relapsed within a year of starting it. About a quarter of the 317 fingolimod patients discontinued at an average of 6.5 months, and 11% relapsed. About 9% of dimethyl fumarate patients, but 6% of fingolimod patients, had new gadolinium-enhancing (GdE) brain lesions at 12 months.
A propensity score analysis was performed to control for confounders; patients were matched one to one for baseline demographics and clinical and MRI characteristics. Dimethyl fumarate patients were almost three times more likely than fingolimod patients to have new GdE lesions after a year (odds ratio, 2.90; 95% confidence interval, 1.24-6.57). They also had an earlier time to discontinuation (OR, 1.35; 95% CI, 1.05-1.74) and clinical relapse (OR, 1.64; 95% CI, 1.10-2.46). The study included patients with secondary progressive disease. Results were the same when the analysis was limited to relapsing-remitting multiple sclerosis.
The investigators concluded that “dimethyl fumarate and fingolimod have comparable annualized relapse rates, overall brain MRI activity, and discontinuation at 12 months.” However, “dimethyl fumarate may have greater GdE lesions and side effects early after treatment initiation, leading to early discontinuation and relapses.
“This makes sense from what we are seeing in the clinic. We know Tecfidera patients have tolerability issues,” especially with gastrointestinal and flushing events, “so they discontinue earlier or might not be as adherent, and so they relapse earlier. The new enhancing lesions might be a difference in efficacy,” Dr. Hersh said.
Patients treated with fingolimod were more likely to be white (91% vs. 83%), have a longer disease duration (16 vs. 14 years), have a higher proportion of relapsing-remitting disease (82% vs. 74%), and have more severe baseline brain lesion burden (15% vs. 8%). The subjects had tried interferon, glatiramer acetate (Copaxone), natalizumab (Tysabri), or other options before being switched to the study medications because of disease activity or intolerability. Patients were in their 40s, on average, and about 70% were women.
Data are now being collected for a 2-year analysis.
There was no industry funding for the work, and Dr. Hersh had no disclosures. Other investigators reported ties to both Novartis, the maker of Gilenya, and Biogen, the maker of Tecfidera.
VANCOUVER – Multiple sclerosis patients discontinued treatment and relapsed earlier with dimethyl fumarate (Tecfidera) than with fingolimod (Gilenya), and had more gadolinium-enhancing lesions at 12 months, in a propensity score matching analysis involving 775 patients at the Cleveland Clinic.
“Based on these data, I now [favor] Gilenya over Tecfidera; Gilenya works a little bit better,” lead investigator and staff neurologist Carrie Hersh said at the annual meeting of the American Academy of Neurology.
The two drugs performed about equally in clinical trials, but Dr. Hersh and her colleagues said fingolimod seems to have the edge in clinical practice; they wanted to see if that hunch held up to scrutiny.
In the single-center cohort study, about 30% of the 458 dimethyl fumarate patients discontinued the drug after an average of 4 months, and about 14% relapsed within a year of starting it. About a quarter of the 317 fingolimod patients discontinued at an average of 6.5 months, and 11% relapsed. About 9% of dimethyl fumarate patients, but 6% of fingolimod patients, had new gadolinium-enhancing (GdE) brain lesions at 12 months.
A propensity score analysis was performed to control for confounders; patients were matched one to one for baseline demographics and clinical and MRI characteristics. Dimethyl fumarate patients were almost three times more likely than fingolimod patients to have new GdE lesions after a year (odds ratio, 2.90; 95% confidence interval, 1.24-6.57). They also had an earlier time to discontinuation (OR, 1.35; 95% CI, 1.05-1.74) and clinical relapse (OR, 1.64; 95% CI, 1.10-2.46). The study included patients with secondary progressive disease. Results were the same when the analysis was limited to relapsing-remitting multiple sclerosis.
The investigators concluded that “dimethyl fumarate and fingolimod have comparable annualized relapse rates, overall brain MRI activity, and discontinuation at 12 months.” However, “dimethyl fumarate may have greater GdE lesions and side effects early after treatment initiation, leading to early discontinuation and relapses.
“This makes sense from what we are seeing in the clinic. We know Tecfidera patients have tolerability issues,” especially with gastrointestinal and flushing events, “so they discontinue earlier or might not be as adherent, and so they relapse earlier. The new enhancing lesions might be a difference in efficacy,” Dr. Hersh said.
Patients treated with fingolimod were more likely to be white (91% vs. 83%), have a longer disease duration (16 vs. 14 years), have a higher proportion of relapsing-remitting disease (82% vs. 74%), and have more severe baseline brain lesion burden (15% vs. 8%). The subjects had tried interferon, glatiramer acetate (Copaxone), natalizumab (Tysabri), or other options before being switched to the study medications because of disease activity or intolerability. Patients were in their 40s, on average, and about 70% were women.
Data are now being collected for a 2-year analysis.
There was no industry funding for the work, and Dr. Hersh had no disclosures. Other investigators reported ties to both Novartis, the maker of Gilenya, and Biogen, the maker of Tecfidera.
VANCOUVER – Multiple sclerosis patients discontinued treatment and relapsed earlier with dimethyl fumarate (Tecfidera) than with fingolimod (Gilenya), and had more gadolinium-enhancing lesions at 12 months, in a propensity score matching analysis involving 775 patients at the Cleveland Clinic.
“Based on these data, I now [favor] Gilenya over Tecfidera; Gilenya works a little bit better,” lead investigator and staff neurologist Carrie Hersh said at the annual meeting of the American Academy of Neurology.
The two drugs performed about equally in clinical trials, but Dr. Hersh and her colleagues said fingolimod seems to have the edge in clinical practice; they wanted to see if that hunch held up to scrutiny.
In the single-center cohort study, about 30% of the 458 dimethyl fumarate patients discontinued the drug after an average of 4 months, and about 14% relapsed within a year of starting it. About a quarter of the 317 fingolimod patients discontinued at an average of 6.5 months, and 11% relapsed. About 9% of dimethyl fumarate patients, but 6% of fingolimod patients, had new gadolinium-enhancing (GdE) brain lesions at 12 months.
A propensity score analysis was performed to control for confounders; patients were matched one to one for baseline demographics and clinical and MRI characteristics. Dimethyl fumarate patients were almost three times more likely than fingolimod patients to have new GdE lesions after a year (odds ratio, 2.90; 95% confidence interval, 1.24-6.57). They also had an earlier time to discontinuation (OR, 1.35; 95% CI, 1.05-1.74) and clinical relapse (OR, 1.64; 95% CI, 1.10-2.46). The study included patients with secondary progressive disease. Results were the same when the analysis was limited to relapsing-remitting multiple sclerosis.
The investigators concluded that “dimethyl fumarate and fingolimod have comparable annualized relapse rates, overall brain MRI activity, and discontinuation at 12 months.” However, “dimethyl fumarate may have greater GdE lesions and side effects early after treatment initiation, leading to early discontinuation and relapses.
“This makes sense from what we are seeing in the clinic. We know Tecfidera patients have tolerability issues,” especially with gastrointestinal and flushing events, “so they discontinue earlier or might not be as adherent, and so they relapse earlier. The new enhancing lesions might be a difference in efficacy,” Dr. Hersh said.
Patients treated with fingolimod were more likely to be white (91% vs. 83%), have a longer disease duration (16 vs. 14 years), have a higher proportion of relapsing-remitting disease (82% vs. 74%), and have more severe baseline brain lesion burden (15% vs. 8%). The subjects had tried interferon, glatiramer acetate (Copaxone), natalizumab (Tysabri), or other options before being switched to the study medications because of disease activity or intolerability. Patients were in their 40s, on average, and about 70% were women.
Data are now being collected for a 2-year analysis.
There was no industry funding for the work, and Dr. Hersh had no disclosures. Other investigators reported ties to both Novartis, the maker of Gilenya, and Biogen, the maker of Tecfidera.
AT THE AAN 2016 ANNUAL MEETING
Key clinical point: Multiple sclerosis patients discontinued treatment and relapsed earlier when treated with dimethyl fumarate (Tecfidera) than with fingolimod (Gilenya), and had more gadolinium-enhancing lesions at 12 months.
Major finding: Dimethyl fumarate patients were almost three times more likely than fingolimod patients to have new GdE lesions after a year (OR, 2.90; 95% CI, 1.24-6.57). They also had an earlier time to discontinuation (OR, 1.35; 95% CI, 1.05-1.74) and clinical relapse (OR, 1.64; 95% CI, 1.10-2.46).
Data source: A propensity score matching analysis involving 775 multiple sclerosis patients at the Cleveland Clinic.
Disclosures: There was no industry funding for the work, and the lead investigator had no disclosures. Other investigators reported ties to both Novartis, the maker of Gilenya, and Biogen, the maker of Tecfidera.
Antithrombotics appear safe in BCVI with concomitant injuries
SAN ANTONIO – Don’t withhold antiplatelet or heparin therapy in patients with blunt cerebrovascular injury, even if they have concomitant traumatic brain or solid organ injuries, advised researchers from the University of Tennessee Health Science Center, Memphis.
With close monitoring, “initiation of early antithrombotic therapy for patients with BCVI [blunt cerebrovascular injury] and concomitant TBI [traumatic brain injury] or SOI [solid organ injury] does not increase the risk of worsening TBI or SOI above baseline.” It is safe, effective, and “should not be withheld,” the researchers concluded after a review of 119 BCVI patients with concomitant injuries.
Seventy four (62%) had TBIs, 26 (22%) had SOIs, and 19 (16%) had both. At some institutions, antithrombotic therapy – the mainstay for BCVI to prevent secondary ischemic stroke – would have been delayed or withheld for fear of triggering hemorrhagic complications.
But at the Health Science Center in Memphis, “we have an extremely cooperative group of neurosurgeons who take BCVI as seriously as we do, and actually allow us, more often than not, to start antithrombotic therapy pretty much immediately after the injury is identified,” investigator and surgery resident Dr. Charles Shahan said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.
As a result, 85 patients (71%) received heparin infusions with goal-activated partial thromboplastin times of 45-60 seconds, and the rest antiplatelet therapy, typically 81-mg aspirin. The center generally uses heparin for TBI patients because of its short half-life, and aspirin for others.
Antithrombosed BCVI patients did as well as did historical controls. TBIs deteriorated – meaning worsening on clinical or CT exam, or delayed operative intervention – in 7%, vs. 10% of TBI patients without BCVI (P = .34). Three percent of SOI patients had delayed laparotomies vs. 5% of SOI patients without BCVI (P = .54). None of the BCVI patients stopped antithrombotics because of complications.
The results held regardless of the type of TBI, SOI, or antithrombotic used.
Overall, 11 patients (9%) had BCVI-related strokes. Without antithrombotic therapy, stroke rates in BCVI can approach 40%.
“Our extremely early use of antithrombotic therapy does not appear to increase our rate of worsening of our hemorrhagic injures and also gets our stroke rate within acceptable limits,” Dr. Shahan said.
The mean age in the study was 38, and just over half the subjects were men.
Dr. Shahan had no disclosures
SAN ANTONIO – Don’t withhold antiplatelet or heparin therapy in patients with blunt cerebrovascular injury, even if they have concomitant traumatic brain or solid organ injuries, advised researchers from the University of Tennessee Health Science Center, Memphis.
With close monitoring, “initiation of early antithrombotic therapy for patients with BCVI [blunt cerebrovascular injury] and concomitant TBI [traumatic brain injury] or SOI [solid organ injury] does not increase the risk of worsening TBI or SOI above baseline.” It is safe, effective, and “should not be withheld,” the researchers concluded after a review of 119 BCVI patients with concomitant injuries.
Seventy four (62%) had TBIs, 26 (22%) had SOIs, and 19 (16%) had both. At some institutions, antithrombotic therapy – the mainstay for BCVI to prevent secondary ischemic stroke – would have been delayed or withheld for fear of triggering hemorrhagic complications.
But at the Health Science Center in Memphis, “we have an extremely cooperative group of neurosurgeons who take BCVI as seriously as we do, and actually allow us, more often than not, to start antithrombotic therapy pretty much immediately after the injury is identified,” investigator and surgery resident Dr. Charles Shahan said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.
As a result, 85 patients (71%) received heparin infusions with goal-activated partial thromboplastin times of 45-60 seconds, and the rest antiplatelet therapy, typically 81-mg aspirin. The center generally uses heparin for TBI patients because of its short half-life, and aspirin for others.
Antithrombosed BCVI patients did as well as did historical controls. TBIs deteriorated – meaning worsening on clinical or CT exam, or delayed operative intervention – in 7%, vs. 10% of TBI patients without BCVI (P = .34). Three percent of SOI patients had delayed laparotomies vs. 5% of SOI patients without BCVI (P = .54). None of the BCVI patients stopped antithrombotics because of complications.
The results held regardless of the type of TBI, SOI, or antithrombotic used.
Overall, 11 patients (9%) had BCVI-related strokes. Without antithrombotic therapy, stroke rates in BCVI can approach 40%.
“Our extremely early use of antithrombotic therapy does not appear to increase our rate of worsening of our hemorrhagic injures and also gets our stroke rate within acceptable limits,” Dr. Shahan said.
The mean age in the study was 38, and just over half the subjects were men.
Dr. Shahan had no disclosures
SAN ANTONIO – Don’t withhold antiplatelet or heparin therapy in patients with blunt cerebrovascular injury, even if they have concomitant traumatic brain or solid organ injuries, advised researchers from the University of Tennessee Health Science Center, Memphis.
With close monitoring, “initiation of early antithrombotic therapy for patients with BCVI [blunt cerebrovascular injury] and concomitant TBI [traumatic brain injury] or SOI [solid organ injury] does not increase the risk of worsening TBI or SOI above baseline.” It is safe, effective, and “should not be withheld,” the researchers concluded after a review of 119 BCVI patients with concomitant injuries.
Seventy four (62%) had TBIs, 26 (22%) had SOIs, and 19 (16%) had both. At some institutions, antithrombotic therapy – the mainstay for BCVI to prevent secondary ischemic stroke – would have been delayed or withheld for fear of triggering hemorrhagic complications.
But at the Health Science Center in Memphis, “we have an extremely cooperative group of neurosurgeons who take BCVI as seriously as we do, and actually allow us, more often than not, to start antithrombotic therapy pretty much immediately after the injury is identified,” investigator and surgery resident Dr. Charles Shahan said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.
As a result, 85 patients (71%) received heparin infusions with goal-activated partial thromboplastin times of 45-60 seconds, and the rest antiplatelet therapy, typically 81-mg aspirin. The center generally uses heparin for TBI patients because of its short half-life, and aspirin for others.
Antithrombosed BCVI patients did as well as did historical controls. TBIs deteriorated – meaning worsening on clinical or CT exam, or delayed operative intervention – in 7%, vs. 10% of TBI patients without BCVI (P = .34). Three percent of SOI patients had delayed laparotomies vs. 5% of SOI patients without BCVI (P = .54). None of the BCVI patients stopped antithrombotics because of complications.
The results held regardless of the type of TBI, SOI, or antithrombotic used.
Overall, 11 patients (9%) had BCVI-related strokes. Without antithrombotic therapy, stroke rates in BCVI can approach 40%.
“Our extremely early use of antithrombotic therapy does not appear to increase our rate of worsening of our hemorrhagic injures and also gets our stroke rate within acceptable limits,” Dr. Shahan said.
The mean age in the study was 38, and just over half the subjects were men.
Dr. Shahan had no disclosures
AT THE EAST SCIENTIFIC ASSEMBLY
Key clinical point: Antithrombotics for BCVI do not make concomitant brain and solid organ injuries worse.
Major finding: TBIs deteriorated in 7% of BCVI patients on heparin infusion, versus 10% of TBI patients without BCVI (P = .34).
Data source: Review of 119 BCVI patients.
Disclosures: The lead investigator had no disclosures.
Extended-release amantadine may improve levodopa dyskinesia control
VANCOUVER – An extended-release amantadine formulation reduced levodopa-induced dyskinesia in a phase III Parkinson’s disease trial from the drug’s developer, Adamas Pharmaceuticals.
Amantadine extended release (ER) is a once-daily, 340-mg capsule taken at bedtime. Patients wake up with the drug on board and achieve peak plasma concentrations during the waking hours. Concentrations drop off in the evening, which might help with sleep, said investigator Dr. Rajesh Pahwa, a neurology professor at the University of Kansas Medical Center, Kansas City.
Generic immediate-release amantadine is usually dosed at 100 mg twice daily, “but 200 mg is [often] not an effective dose” for levodopa-induced dyskinesia, Dr. Pahwa noted. “The effective dose is closer to 340 mg.”
It’s hoped that the ER formulation, by smoothing out the peaks and troughs in plasma concentrations, might make higher dosing more tolerable, he said at the annual meeting of the American Academy of Neurology.
The study randomized 126 patients with Parkinson’s disease and levodopa dyskinesia evenly to placebo or amantadine ER for 24 weeks.
Compared with placebo and based on patient diaries, amantadine ER reduced on-time with troublesome dyskinesias by about 1.5 hours per day, from a baseline of about 4.6 hours. Amantadine ER also increased on-time without troublesome dyskinesias by about 2.5 hours, from a baseline of about 8.4 hours, and reduced off-time by almost an hour, from a baseline of about 3.1 hours – with the greatest benefits coming at 12 weeks.
The drug also reduced Unified Dyskinesia Rating Scale scores about 8 points over placebo at week 12, and 9 points at week 24, from a baseline mean of about 40 points. At week 12, 60% of the ER patients, compared with 19% of placebo subjects, had moderately to markedly improved scores on the Clinical Global Impression of Change. Pharmacokinetics were not reported.
“All the efficacy parameters are going in the same direction,” Dr. Pahwa said.
About 21% of amantadine ER patients dropped out of the study because of side effects, most frequently hallucinations, peripheral edema, dizziness, dry mouth, constipation, and falls. Side effects led to the withdrawal of about 7% of placebo patients.
“We had some dropouts, but at least we were able to show that the majority of patients were able to tolerate 340 mg and have efficacy,” Dr. Pahwa said.
Food and Drug Administration labeling of an immediate-release amantadine formulation reported nausea, dizziness, and insomnia in up to 10% of patients, with more serious side effects in fewer patients, in doses generally of 100 mg twice daily.
Adamas plans to submit an approval package to the FDA in 2016, with possible amantadine ER approval in 2017.
The trial excluded patients who had used immediate-release amantadine within 30 days, along with people who had deep brain stimulation and those who had hallucinated within a year for any reason.
The mean baseline levodopa dose was 862 mg, and mean duration of levodopa-induced dyskinesia was about 4 years. The mean age of patients in the trial was 65 years.
Adamas Pharmaceuticals funded the study. Dr. Pahwa is a paid consultant and a researcher for the company.
VANCOUVER – An extended-release amantadine formulation reduced levodopa-induced dyskinesia in a phase III Parkinson’s disease trial from the drug’s developer, Adamas Pharmaceuticals.
Amantadine extended release (ER) is a once-daily, 340-mg capsule taken at bedtime. Patients wake up with the drug on board and achieve peak plasma concentrations during the waking hours. Concentrations drop off in the evening, which might help with sleep, said investigator Dr. Rajesh Pahwa, a neurology professor at the University of Kansas Medical Center, Kansas City.
Generic immediate-release amantadine is usually dosed at 100 mg twice daily, “but 200 mg is [often] not an effective dose” for levodopa-induced dyskinesia, Dr. Pahwa noted. “The effective dose is closer to 340 mg.”
It’s hoped that the ER formulation, by smoothing out the peaks and troughs in plasma concentrations, might make higher dosing more tolerable, he said at the annual meeting of the American Academy of Neurology.
The study randomized 126 patients with Parkinson’s disease and levodopa dyskinesia evenly to placebo or amantadine ER for 24 weeks.
Compared with placebo and based on patient diaries, amantadine ER reduced on-time with troublesome dyskinesias by about 1.5 hours per day, from a baseline of about 4.6 hours. Amantadine ER also increased on-time without troublesome dyskinesias by about 2.5 hours, from a baseline of about 8.4 hours, and reduced off-time by almost an hour, from a baseline of about 3.1 hours – with the greatest benefits coming at 12 weeks.
The drug also reduced Unified Dyskinesia Rating Scale scores about 8 points over placebo at week 12, and 9 points at week 24, from a baseline mean of about 40 points. At week 12, 60% of the ER patients, compared with 19% of placebo subjects, had moderately to markedly improved scores on the Clinical Global Impression of Change. Pharmacokinetics were not reported.
“All the efficacy parameters are going in the same direction,” Dr. Pahwa said.
About 21% of amantadine ER patients dropped out of the study because of side effects, most frequently hallucinations, peripheral edema, dizziness, dry mouth, constipation, and falls. Side effects led to the withdrawal of about 7% of placebo patients.
“We had some dropouts, but at least we were able to show that the majority of patients were able to tolerate 340 mg and have efficacy,” Dr. Pahwa said.
Food and Drug Administration labeling of an immediate-release amantadine formulation reported nausea, dizziness, and insomnia in up to 10% of patients, with more serious side effects in fewer patients, in doses generally of 100 mg twice daily.
Adamas plans to submit an approval package to the FDA in 2016, with possible amantadine ER approval in 2017.
The trial excluded patients who had used immediate-release amantadine within 30 days, along with people who had deep brain stimulation and those who had hallucinated within a year for any reason.
The mean baseline levodopa dose was 862 mg, and mean duration of levodopa-induced dyskinesia was about 4 years. The mean age of patients in the trial was 65 years.
Adamas Pharmaceuticals funded the study. Dr. Pahwa is a paid consultant and a researcher for the company.
VANCOUVER – An extended-release amantadine formulation reduced levodopa-induced dyskinesia in a phase III Parkinson’s disease trial from the drug’s developer, Adamas Pharmaceuticals.
Amantadine extended release (ER) is a once-daily, 340-mg capsule taken at bedtime. Patients wake up with the drug on board and achieve peak plasma concentrations during the waking hours. Concentrations drop off in the evening, which might help with sleep, said investigator Dr. Rajesh Pahwa, a neurology professor at the University of Kansas Medical Center, Kansas City.
Generic immediate-release amantadine is usually dosed at 100 mg twice daily, “but 200 mg is [often] not an effective dose” for levodopa-induced dyskinesia, Dr. Pahwa noted. “The effective dose is closer to 340 mg.”
It’s hoped that the ER formulation, by smoothing out the peaks and troughs in plasma concentrations, might make higher dosing more tolerable, he said at the annual meeting of the American Academy of Neurology.
The study randomized 126 patients with Parkinson’s disease and levodopa dyskinesia evenly to placebo or amantadine ER for 24 weeks.
Compared with placebo and based on patient diaries, amantadine ER reduced on-time with troublesome dyskinesias by about 1.5 hours per day, from a baseline of about 4.6 hours. Amantadine ER also increased on-time without troublesome dyskinesias by about 2.5 hours, from a baseline of about 8.4 hours, and reduced off-time by almost an hour, from a baseline of about 3.1 hours – with the greatest benefits coming at 12 weeks.
The drug also reduced Unified Dyskinesia Rating Scale scores about 8 points over placebo at week 12, and 9 points at week 24, from a baseline mean of about 40 points. At week 12, 60% of the ER patients, compared with 19% of placebo subjects, had moderately to markedly improved scores on the Clinical Global Impression of Change. Pharmacokinetics were not reported.
“All the efficacy parameters are going in the same direction,” Dr. Pahwa said.
About 21% of amantadine ER patients dropped out of the study because of side effects, most frequently hallucinations, peripheral edema, dizziness, dry mouth, constipation, and falls. Side effects led to the withdrawal of about 7% of placebo patients.
“We had some dropouts, but at least we were able to show that the majority of patients were able to tolerate 340 mg and have efficacy,” Dr. Pahwa said.
Food and Drug Administration labeling of an immediate-release amantadine formulation reported nausea, dizziness, and insomnia in up to 10% of patients, with more serious side effects in fewer patients, in doses generally of 100 mg twice daily.
Adamas plans to submit an approval package to the FDA in 2016, with possible amantadine ER approval in 2017.
The trial excluded patients who had used immediate-release amantadine within 30 days, along with people who had deep brain stimulation and those who had hallucinated within a year for any reason.
The mean baseline levodopa dose was 862 mg, and mean duration of levodopa-induced dyskinesia was about 4 years. The mean age of patients in the trial was 65 years.
Adamas Pharmaceuticals funded the study. Dr. Pahwa is a paid consultant and a researcher for the company.
AT THE AAN ANNUAL MEETING
Key clinical point: A better amantadine option may be coming soon.
Major finding: Compared with placebo and based on patient diaries, extended-release amantadine reduced on-time with troublesome dyskinesias by about 1.5 hours per day, from a baseline of about 4.6 hours.
Data source: A phase III trial in 126 patients.
Disclosures: Adamas Pharmaceuticals funded the study. Dr. Pahwa is a paid consultant and a researcher for the company.
Small study: OTC antihistamine shows potential as a remyelinating agent in MS
VANCOUVER – Clemastine fumarate (Tavist) reduced delay in visual evoked potentials by 1.9 ms per eye, with a trend toward improved low contrast visual acuity, in a small randomized, placebo-controlled trial of patients with multiple sclerosis and chronic, stable optic neuropathy.
An improvement in visual evoked potential (VEP) transmission delay, the time for signal transmission from the retina to the visual cortex, was considered a marker of myelin repair. To be included in the study, participants had to have a transmission delay of at least 118 ms in one or both eyes
The idea was to assess the remyelination potential of clemastine in patients with multiple sclerosis (MS) and chronic optic neuropathy. “While the improvement in [VEP] appears modest, this study is promising because it is the first time a drug has been shown to possibly reverse the damage done by MS. This study provides a framework for future MS repair studies,” said Dr. Ari Green, assistant clinical director of the University of California, San Francisco (UCSF) Multiple Sclerosis Center.
“We certainly wouldn’t promote this for clinical use, but it’s a promising indication that there’s a potential for remyelination” in MS. “We need to further investigate this,” he said at the annual meeting of the American Academy of Neurology.
A total of 50 patients were randomized to oral clemastine 4 mg twice daily or matched placebo for 3 months, then switched to the opposite arm for 2 months. The dosage was a bit higher than that typically used in adults for allergic disease.
The VEP improvement persisted even when clemastine patients were switched to placebo, which suggests “we were having a remyelinating effect, not just a transient effect on ion channels,” Dr. Green said.
Patients were 40 years old, on average, with mean disease duration of 5 years and mean Expanded Disability Status Scale score of 2.1. They had to have had a bout of optic neuropathy within the previous 5 years, but not within the previous 6 months. They were allowed to stay on their disease-modifying therapies while in the study. Clemastine was associated with mild worsening of fatigue.
Previous studies at UCSF suggest that clemastine is one of several antimuscarinic agents that can induce oligodendrocyte precursor cells (OPC) into mature, myelin-producing cells, which might help account for the findings. The next step in the work is to see how well longer dosing works, and how well clemastine works in acute optic neuropathy. The team also wants to test stronger OPC inducers.
The University of California, San Francisco, funded the work. Dr. Green is an adviser for Bionure, Mylan Pharma, MedImmune, Inception 5, and Novartis, and receives research support from Novartis.
VANCOUVER – Clemastine fumarate (Tavist) reduced delay in visual evoked potentials by 1.9 ms per eye, with a trend toward improved low contrast visual acuity, in a small randomized, placebo-controlled trial of patients with multiple sclerosis and chronic, stable optic neuropathy.
An improvement in visual evoked potential (VEP) transmission delay, the time for signal transmission from the retina to the visual cortex, was considered a marker of myelin repair. To be included in the study, participants had to have a transmission delay of at least 118 ms in one or both eyes
The idea was to assess the remyelination potential of clemastine in patients with multiple sclerosis (MS) and chronic optic neuropathy. “While the improvement in [VEP] appears modest, this study is promising because it is the first time a drug has been shown to possibly reverse the damage done by MS. This study provides a framework for future MS repair studies,” said Dr. Ari Green, assistant clinical director of the University of California, San Francisco (UCSF) Multiple Sclerosis Center.
“We certainly wouldn’t promote this for clinical use, but it’s a promising indication that there’s a potential for remyelination” in MS. “We need to further investigate this,” he said at the annual meeting of the American Academy of Neurology.
A total of 50 patients were randomized to oral clemastine 4 mg twice daily or matched placebo for 3 months, then switched to the opposite arm for 2 months. The dosage was a bit higher than that typically used in adults for allergic disease.
The VEP improvement persisted even when clemastine patients were switched to placebo, which suggests “we were having a remyelinating effect, not just a transient effect on ion channels,” Dr. Green said.
Patients were 40 years old, on average, with mean disease duration of 5 years and mean Expanded Disability Status Scale score of 2.1. They had to have had a bout of optic neuropathy within the previous 5 years, but not within the previous 6 months. They were allowed to stay on their disease-modifying therapies while in the study. Clemastine was associated with mild worsening of fatigue.
Previous studies at UCSF suggest that clemastine is one of several antimuscarinic agents that can induce oligodendrocyte precursor cells (OPC) into mature, myelin-producing cells, which might help account for the findings. The next step in the work is to see how well longer dosing works, and how well clemastine works in acute optic neuropathy. The team also wants to test stronger OPC inducers.
The University of California, San Francisco, funded the work. Dr. Green is an adviser for Bionure, Mylan Pharma, MedImmune, Inception 5, and Novartis, and receives research support from Novartis.
VANCOUVER – Clemastine fumarate (Tavist) reduced delay in visual evoked potentials by 1.9 ms per eye, with a trend toward improved low contrast visual acuity, in a small randomized, placebo-controlled trial of patients with multiple sclerosis and chronic, stable optic neuropathy.
An improvement in visual evoked potential (VEP) transmission delay, the time for signal transmission from the retina to the visual cortex, was considered a marker of myelin repair. To be included in the study, participants had to have a transmission delay of at least 118 ms in one or both eyes
The idea was to assess the remyelination potential of clemastine in patients with multiple sclerosis (MS) and chronic optic neuropathy. “While the improvement in [VEP] appears modest, this study is promising because it is the first time a drug has been shown to possibly reverse the damage done by MS. This study provides a framework for future MS repair studies,” said Dr. Ari Green, assistant clinical director of the University of California, San Francisco (UCSF) Multiple Sclerosis Center.
“We certainly wouldn’t promote this for clinical use, but it’s a promising indication that there’s a potential for remyelination” in MS. “We need to further investigate this,” he said at the annual meeting of the American Academy of Neurology.
A total of 50 patients were randomized to oral clemastine 4 mg twice daily or matched placebo for 3 months, then switched to the opposite arm for 2 months. The dosage was a bit higher than that typically used in adults for allergic disease.
The VEP improvement persisted even when clemastine patients were switched to placebo, which suggests “we were having a remyelinating effect, not just a transient effect on ion channels,” Dr. Green said.
Patients were 40 years old, on average, with mean disease duration of 5 years and mean Expanded Disability Status Scale score of 2.1. They had to have had a bout of optic neuropathy within the previous 5 years, but not within the previous 6 months. They were allowed to stay on their disease-modifying therapies while in the study. Clemastine was associated with mild worsening of fatigue.
Previous studies at UCSF suggest that clemastine is one of several antimuscarinic agents that can induce oligodendrocyte precursor cells (OPC) into mature, myelin-producing cells, which might help account for the findings. The next step in the work is to see how well longer dosing works, and how well clemastine works in acute optic neuropathy. The team also wants to test stronger OPC inducers.
The University of California, San Francisco, funded the work. Dr. Green is an adviser for Bionure, Mylan Pharma, MedImmune, Inception 5, and Novartis, and receives research support from Novartis.
AT THE AAN 2016 ANNUAL MEETING
Key clinical point: Clemastine led to a modest reduction in visual evoked potential delay in MS patients with chronic, stable optic neuropathy.
Major finding: Clemastine fumarate (Tavist) reduced delay in visual evoked potentials by 1.9 ms per eye, with a trend toward improvement of low contrast visual acuity, in MS patients with chronic, stable optic neuropathy.
Data source: Randomized, blinded crossover trial in 50 MS patients.
Disclosures: The University of California, San Francisco, funded the work. Dr. Green is an adviser for Bionure, Mylan Pharma, MedImmune, Inception 5, and Novartis, and receives research support from Novartis.
Bone Marrow Transplant Cures Severe HPV Disease in GATA2 Immunodeficiency
SAN DIEGO – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.
A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.
Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.
While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.
Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.
Natural killer and monocyte cell counts were far below normal at the time of transplant.
SAN DIEGO – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.
A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.
Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.
While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.
Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.
Natural killer and monocyte cell counts were far below normal at the time of transplant.
SAN DIEGO – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.
A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.
Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.
While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.
Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.
Natural killer and monocyte cell counts were far below normal at the time of transplant.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Bone marrow transplant cures severe HPV disease in GATA2 immunodeficiency
SAN DIEGO – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.
A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.
Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.
While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.
Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.
Natural killer and monocyte cell counts were far below normal at the time of transplant.
SAN DIEGO – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.
A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.
Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.
While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.
Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.
Natural killer and monocyte cell counts were far below normal at the time of transplant.
SAN DIEGO – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.
A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.
Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.
While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.
Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.
Natural killer and monocyte cell counts were far below normal at the time of transplant.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Refer women with severe, refractory HPV disease for genetic work-up and possible bone marrow transplant.
Major finding: Twenty-seven (77%) of GATA2 deficient women reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s.
Data source: Review of 35 women with GATA2 mutations.
Disclosures: There was no outside funding for the work. The presenter had no disclosures.
Childhood Obesity Predicted by Infant BMI
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ENDO 2016
VIDEO: Childhood obesity predicted by infant BMI
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Infants above the 85th percentile for body mass index at 6 months are up to nine times more likely to be severely obese by the age of 6, according to a Cincinnati Children’s Hospital investigation.
The finding means that pediatricians should routinely plot and follow body mass index (BMI) from an early age, just like height, weight, and head circumference, said investigator Dr. Allison Smego, an endocrinology fellow.
She and her colleagues reviewed the charts from birth to age 6 of 783 lean children and 480 children above the 99th BMI percentile. BMI started differentiating when children were as young as 4 months old, about a year and half before the onset of clinical obesity. The predictive value of the 85th percentile threshold held at 6, 12, and 18 months. The finding was subsequently validated in over 2,600 children.
In an interview at the annual meeting of the Endocrine Society, Dr. Smego explained how to use the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ENDO 2016
