Richard Hyer

CHICAGO – An extended-release formulation of gabapentin for hot flashes showed the potential both to minimize peak adverse events and to allow for less frequent dosing in a randomized, controlled trial of 565 women, said Dr. Wulf Utian.

“The results of the BREEZE 2 study suggest that gabapentin–extended release 1,800 mg/day may be effective and well tolerated for the treatment of moderate to severe hot flashes in postmenopausal women,” he noted at the meeting.

Gabapentin-ER releases over 8 hours, potentially minimizing peak adverse events and allowing once daily or twice daily dosing, said Dr. Utian, the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology at Case Western Reserve University in Cleveland.

Gabapentin is an anticonvulsant that is also used to relieve nerve-related pain.

BREEZE 2 is a prospective, multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women aged 18-70 years at 45 sites across the United States.

The study had two active arms: gabapentin-ER 1,200 mg given once daily, and 1,800 mg given as 600 mg in the morning and 1,200 in the evening. Efficacy was assessed at 4 and 12 weeks, and the treatment duration was 3 months.

The primary efficacy end points were reductions in the mean frequency of moderate to severe hot flashes and the average severity of hot flashes.

The trial's secondary end points were the proportion of patients categorized as “much improved” or “very much improved” at 12 weeks in the self-reported Patient Global Impression of Change scale. Investigators also recorded their impression of the results of the therapy using the Clinician Global Impression of Change scale.

Postmenopausal women who had been experiencing seven or more moderate to severe hot flashes per day (or at least 50 per week), accompanied by sweating during at least the previous 30 days, were the trial population.

Baseline characteristics were similar across the three groups. In the 1,800-mg group, for example, the average age was 54 years, the women were 71% white, and the average body mass index was less than 30 kg/m

Data were subjected to both parametric and nonparametric analysis, said Dr. Utian, because parametric analyses can be influenced by outliers.

At 4 weeks and 12 weeks, changes in the mean severity of moderate and severe hot flashes were −0.6 and −0.8 for 1,800-mg group, compared with the placebo group; both were significant differences.

More than 60% of patients in both active treatment groups and more than 40% in the placebo group self-reported and were clinician reported as “very much improved” at 12 weeks. “This was a particularly high placebo response,” said Dr. Utian.

Nonparametric analysis showed a statistically significant change in median frequency of moderate to severe hot flashes at 4 weeks and 12 weeks in both active groups, compared with the placebo group.

Dizziness was the most commonly reported adverse event in both the 1,800-mg and 1,200-mg groups, whereas headache was most commonly reported in the placebo group.

Somnolence was the second most common complaint in the active treatment groups.

A total of 48 patients across both active treatment groups discontinued because of adverse events.

“Essentially, this long-release product was well tolerated, adverse events were mild, the difference was a slight difference in dizziness and somnolence during the titration, and [there was] no real difference in the adverse events” between the 1,800-mg and the 1,200-mg dosing regimens, said Dr. Utian.

“The incidence of the adverse events declined markedly after 2-4 weeks of study therapy,” he added.

CHICAGO – An extended-release formulation of gabapentin for hot flashes showed the potential both to minimize peak adverse events and to allow for less frequent dosing in a randomized, controlled trial of 565 women, said Dr. Wulf Utian.

“The results of the BREEZE 2 study suggest that gabapentin–extended release 1,800 mg/day may be effective and well tolerated for the treatment of moderate to severe hot flashes in postmenopausal women,” he noted at the meeting.

Gabapentin-ER releases over 8 hours, potentially minimizing peak adverse events and allowing once daily or twice daily dosing, said Dr. Utian, the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology at Case Western Reserve University in Cleveland.

Gabapentin is an anticonvulsant that is also used to relieve nerve-related pain.

BREEZE 2 is a prospective, multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women aged 18-70 years at 45 sites across the United States.

The study had two active arms: gabapentin-ER 1,200 mg given once daily, and 1,800 mg given as 600 mg in the morning and 1,200 in the evening. Efficacy was assessed at 4 and 12 weeks, and the treatment duration was 3 months.

The primary efficacy end points were reductions in the mean frequency of moderate to severe hot flashes and the average severity of hot flashes.

The trial's secondary end points were the proportion of patients categorized as “much improved” or “very much improved” at 12 weeks in the self-reported Patient Global Impression of Change scale. Investigators also recorded their impression of the results of the therapy using the Clinician Global Impression of Change scale.

Postmenopausal women who had been experiencing seven or more moderate to severe hot flashes per day (or at least 50 per week), accompanied by sweating during at least the previous 30 days, were the trial population.

Baseline characteristics were similar across the three groups. In the 1,800-mg group, for example, the average age was 54 years, the women were 71% white, and the average body mass index was less than 30 kg/m

Data were subjected to both parametric and nonparametric analysis, said Dr. Utian, because parametric analyses can be influenced by outliers.

At 4 weeks and 12 weeks, changes in the mean severity of moderate and severe hot flashes were −0.6 and −0.8 for 1,800-mg group, compared with the placebo group; both were significant differences.

More than 60% of patients in both active treatment groups and more than 40% in the placebo group self-reported and were clinician reported as “very much improved” at 12 weeks. “This was a particularly high placebo response,” said Dr. Utian.

Nonparametric analysis showed a statistically significant change in median frequency of moderate to severe hot flashes at 4 weeks and 12 weeks in both active groups, compared with the placebo group.

Dizziness was the most commonly reported adverse event in both the 1,800-mg and 1,200-mg groups, whereas headache was most commonly reported in the placebo group.

Somnolence was the second most common complaint in the active treatment groups.

A total of 48 patients across both active treatment groups discontinued because of adverse events.

“Essentially, this long-release product was well tolerated, adverse events were mild, the difference was a slight difference in dizziness and somnolence during the titration, and [there was] no real difference in the adverse events” between the 1,800-mg and the 1,200-mg dosing regimens, said Dr. Utian.

“The incidence of the adverse events declined markedly after 2-4 weeks of study therapy,” he added.

CHICAGO – An extended-release formulation of gabapentin for hot flashes showed the potential both to minimize peak adverse events and to allow for less frequent dosing in a randomized, controlled trial of 565 women, said Dr. Wulf Utian.

“The results of the BREEZE 2 study suggest that gabapentin–extended release 1,800 mg/day may be effective and well tolerated for the treatment of moderate to severe hot flashes in postmenopausal women,” he noted at the meeting.

Gabapentin-ER releases over 8 hours, potentially minimizing peak adverse events and allowing once daily or twice daily dosing, said Dr. Utian, the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology at Case Western Reserve University in Cleveland.

Gabapentin is an anticonvulsant that is also used to relieve nerve-related pain.

BREEZE 2 is a prospective, multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women aged 18-70 years at 45 sites across the United States.

The study had two active arms: gabapentin-ER 1,200 mg given once daily, and 1,800 mg given as 600 mg in the morning and 1,200 in the evening. Efficacy was assessed at 4 and 12 weeks, and the treatment duration was 3 months.

The primary efficacy end points were reductions in the mean frequency of moderate to severe hot flashes and the average severity of hot flashes.

The trial's secondary end points were the proportion of patients categorized as “much improved” or “very much improved” at 12 weeks in the self-reported Patient Global Impression of Change scale. Investigators also recorded their impression of the results of the therapy using the Clinician Global Impression of Change scale.

Postmenopausal women who had been experiencing seven or more moderate to severe hot flashes per day (or at least 50 per week), accompanied by sweating during at least the previous 30 days, were the trial population.

Baseline characteristics were similar across the three groups. In the 1,800-mg group, for example, the average age was 54 years, the women were 71% white, and the average body mass index was less than 30 kg/m

Data were subjected to both parametric and nonparametric analysis, said Dr. Utian, because parametric analyses can be influenced by outliers.

At 4 weeks and 12 weeks, changes in the mean severity of moderate and severe hot flashes were −0.6 and −0.8 for 1,800-mg group, compared with the placebo group; both were significant differences.

More than 60% of patients in both active treatment groups and more than 40% in the placebo group self-reported and were clinician reported as “very much improved” at 12 weeks. “This was a particularly high placebo response,” said Dr. Utian.

Nonparametric analysis showed a statistically significant change in median frequency of moderate to severe hot flashes at 4 weeks and 12 weeks in both active groups, compared with the placebo group.

Dizziness was the most commonly reported adverse event in both the 1,800-mg and 1,200-mg groups, whereas headache was most commonly reported in the placebo group.

Somnolence was the second most common complaint in the active treatment groups.

A total of 48 patients across both active treatment groups discontinued because of adverse events.

“Essentially, this long-release product was well tolerated, adverse events were mild, the difference was a slight difference in dizziness and somnolence during the titration, and [there was] no real difference in the adverse events” between the 1,800-mg and the 1,200-mg dosing regimens, said Dr. Utian.

“The incidence of the adverse events declined markedly after 2-4 weeks of study therapy,” he added.

CHICAGO – The results of the Women’s Health Initiative randomized clinical trial suggest that postmenopausal women who begin hormone therapy may be putting themselves at risk for coronary heart disease, but a new study from the University of Oklahoma Health Sciences Center suggests that the presence or absence of the metabolic syndrome at baseline is a key determining factor.

"What we found is that if the metabolic syndrome was present, indeed there was a greater risk, greater odds of event, and this was statistically significant. In contrast, if no metabolic syndrome was present, there was no increased risk," said principal investigator Dr. Robert Wild, professor of ob.gyn. and adjunct professor of medicine–cardiology at the center.

The nested case-control study examined the Women’s Health Initiative cohort for an effect modification between elevated baseline risk and hormone therapy (HT). It found 359 incident cases of coronary heart disease (CHD), and matched these to 817 controls without CHD. Controls were matched with a variety of criteria, including prevalent cardiovascular disease at baseline. Trials of estrogen plus progesterone and estrogen alone were analyzed separately and in a pooled analysis.

Metabolic syndrome was defined by ATP (Adult Treatment Panel) III criteria, where three of the following five criteria are met: elevated waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose.

In the pooled trial analysis of estrogen plus progesterone and estrogen alone, the metabolic syndrome was found to be an effect modifier. The odds ratio for treatment effect was 0.98 for women without the metabolic syndrome and 1.72 for those with the metabolic syndrome.

The individual trials had limited power, said Dr. Wild, but the findings were similar.

"Women without metabolic syndrome had no increase in risk of coronary heart disease vs. placebo, whereas women with metabolic syndrome had elevated risk," said Dr. Wild.

The reasons for this heightened risk might be more advanced stages of atherosclerosis and a heightened thrombogenic state among women with the metabolic syndrome, he said.

"Baseline CHD risk assessment may be helpful to identify women at increased risk for CHD when taking hormone therapy," said Dr. Wild.

Dr. Wild disclosed no significant financial relationships. This study was sponsored by the University of Oklahoma Health Sciences Center, Oklahoma City.

CHICAGO – The results of the Women’s Health Initiative randomized clinical trial suggest that postmenopausal women who begin hormone therapy may be putting themselves at risk for coronary heart disease, but a new study from the University of Oklahoma Health Sciences Center suggests that the presence or absence of the metabolic syndrome at baseline is a key determining factor.

"What we found is that if the metabolic syndrome was present, indeed there was a greater risk, greater odds of event, and this was statistically significant. In contrast, if no metabolic syndrome was present, there was no increased risk," said principal investigator Dr. Robert Wild, professor of ob.gyn. and adjunct professor of medicine–cardiology at the center.

The nested case-control study examined the Women’s Health Initiative cohort for an effect modification between elevated baseline risk and hormone therapy (HT). It found 359 incident cases of coronary heart disease (CHD), and matched these to 817 controls without CHD. Controls were matched with a variety of criteria, including prevalent cardiovascular disease at baseline. Trials of estrogen plus progesterone and estrogen alone were analyzed separately and in a pooled analysis.

Metabolic syndrome was defined by ATP (Adult Treatment Panel) III criteria, where three of the following five criteria are met: elevated waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose.

In the pooled trial analysis of estrogen plus progesterone and estrogen alone, the metabolic syndrome was found to be an effect modifier. The odds ratio for treatment effect was 0.98 for women without the metabolic syndrome and 1.72 for those with the metabolic syndrome.

The individual trials had limited power, said Dr. Wild, but the findings were similar.

"Women without metabolic syndrome had no increase in risk of coronary heart disease vs. placebo, whereas women with metabolic syndrome had elevated risk," said Dr. Wild.

The reasons for this heightened risk might be more advanced stages of atherosclerosis and a heightened thrombogenic state among women with the metabolic syndrome, he said.

"Baseline CHD risk assessment may be helpful to identify women at increased risk for CHD when taking hormone therapy," said Dr. Wild.

Dr. Wild disclosed no significant financial relationships. This study was sponsored by the University of Oklahoma Health Sciences Center, Oklahoma City.

CHICAGO – The results of the Women’s Health Initiative randomized clinical trial suggest that postmenopausal women who begin hormone therapy may be putting themselves at risk for coronary heart disease, but a new study from the University of Oklahoma Health Sciences Center suggests that the presence or absence of the metabolic syndrome at baseline is a key determining factor.

"What we found is that if the metabolic syndrome was present, indeed there was a greater risk, greater odds of event, and this was statistically significant. In contrast, if no metabolic syndrome was present, there was no increased risk," said principal investigator Dr. Robert Wild, professor of ob.gyn. and adjunct professor of medicine–cardiology at the center.

The nested case-control study examined the Women’s Health Initiative cohort for an effect modification between elevated baseline risk and hormone therapy (HT). It found 359 incident cases of coronary heart disease (CHD), and matched these to 817 controls without CHD. Controls were matched with a variety of criteria, including prevalent cardiovascular disease at baseline. Trials of estrogen plus progesterone and estrogen alone were analyzed separately and in a pooled analysis.

Metabolic syndrome was defined by ATP (Adult Treatment Panel) III criteria, where three of the following five criteria are met: elevated waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose.

In the pooled trial analysis of estrogen plus progesterone and estrogen alone, the metabolic syndrome was found to be an effect modifier. The odds ratio for treatment effect was 0.98 for women without the metabolic syndrome and 1.72 for those with the metabolic syndrome.

The individual trials had limited power, said Dr. Wild, but the findings were similar.

"Women without metabolic syndrome had no increase in risk of coronary heart disease vs. placebo, whereas women with metabolic syndrome had elevated risk," said Dr. Wild.

The reasons for this heightened risk might be more advanced stages of atherosclerosis and a heightened thrombogenic state among women with the metabolic syndrome, he said.

"Baseline CHD risk assessment may be helpful to identify women at increased risk for CHD when taking hormone therapy," said Dr. Wild.

Dr. Wild disclosed no significant financial relationships. This study was sponsored by the University of Oklahoma Health Sciences Center, Oklahoma City.

CHICAGO – The results of the Women’s Health Initiative randomized clinical trial suggest that postmenopausal women who begin hormone therapy may be putting themselves at risk for coronary heart disease, but a new study from the University of Oklahoma Health Sciences Center suggests that the presence or absence of the metabolic syndrome at baseline is a key determining factor.

"What we found is that if the metabolic syndrome was present, indeed there was a greater risk, greater odds of event, and this was statistically significant. In contrast, if no metabolic syndrome was present, there was no increased risk," said principal investigator Dr. Robert Wild, professor of ob.gyn. and adjunct professor of medicine–cardiology at the center.

The nested case-control study examined the Women’s Health Initiative cohort for an effect modification between elevated baseline risk and hormone therapy (HT). It found 359 incident cases of coronary heart disease (CHD), and matched these to 817 controls without CHD. Controls were matched with a variety of criteria, including prevalent cardiovascular disease at baseline. Trials of estrogen plus progesterone and estrogen alone were analyzed separately and in a pooled analysis.

Metabolic syndrome was defined by ATP (Adult Treatment Panel) III criteria, where three of the following five criteria are met: elevated waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose.

In the pooled trial analysis of estrogen plus progesterone and estrogen alone, the metabolic syndrome was found to be an effect modifier. The odds ratio for treatment effect was 0.98 for women without the metabolic syndrome and 1.72 for those with the metabolic syndrome.

The individual trials had limited power, said Dr. Wild, but the findings were similar.

"Women without metabolic syndrome had no increase in risk of coronary heart disease vs. placebo, whereas women with metabolic syndrome had elevated risk," said Dr. Wild.

The reasons for this heightened risk might be more advanced stages of atherosclerosis and a heightened thrombogenic state among women with the metabolic syndrome, he said.

"Baseline CHD risk assessment may be helpful to identify women at increased risk for CHD when taking hormone therapy," said Dr. Wild.

Dr. Wild disclosed no significant financial relationships. This study was sponsored by the University of Oklahoma Health Sciences Center, Oklahoma City.

CHICAGO – The results of the Women’s Health Initiative randomized clinical trial suggest that postmenopausal women who begin hormone therapy may be putting themselves at risk for coronary heart disease, but a new study from the University of Oklahoma Health Sciences Center suggests that the presence or absence of the metabolic syndrome at baseline is a key determining factor.

"What we found is that if the metabolic syndrome was present, indeed there was a greater risk, greater odds of event, and this was statistically significant. In contrast, if no metabolic syndrome was present, there was no increased risk," said principal investigator Dr. Robert Wild, professor of ob.gyn. and adjunct professor of medicine–cardiology at the center.

The nested case-control study examined the Women’s Health Initiative cohort for an effect modification between elevated baseline risk and hormone therapy (HT). It found 359 incident cases of coronary heart disease (CHD), and matched these to 817 controls without CHD. Controls were matched with a variety of criteria, including prevalent cardiovascular disease at baseline. Trials of estrogen plus progesterone and estrogen alone were analyzed separately and in a pooled analysis.

Metabolic syndrome was defined by ATP (Adult Treatment Panel) III criteria, where three of the following five criteria are met: elevated waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose.

In the pooled trial analysis of estrogen plus progesterone and estrogen alone, the metabolic syndrome was found to be an effect modifier. The odds ratio for treatment effect was 0.98 for women without the metabolic syndrome and 1.72 for those with the metabolic syndrome.

The individual trials had limited power, said Dr. Wild, but the findings were similar.

"Women without metabolic syndrome had no increase in risk of coronary heart disease vs. placebo, whereas women with metabolic syndrome had elevated risk," said Dr. Wild.

The reasons for this heightened risk might be more advanced stages of atherosclerosis and a heightened thrombogenic state among women with the metabolic syndrome, he said.

"Baseline CHD risk assessment may be helpful to identify women at increased risk for CHD when taking hormone therapy," said Dr. Wild.

Dr. Wild disclosed no significant financial relationships. This study was sponsored by the University of Oklahoma Health Sciences Center, Oklahoma City.

CHICAGO – The results of the Women’s Health Initiative randomized clinical trial suggest that postmenopausal women who begin hormone therapy may be putting themselves at risk for coronary heart disease, but a new study from the University of Oklahoma Health Sciences Center suggests that the presence or absence of the metabolic syndrome at baseline is a key determining factor.

"What we found is that if the metabolic syndrome was present, indeed there was a greater risk, greater odds of event, and this was statistically significant. In contrast, if no metabolic syndrome was present, there was no increased risk," said principal investigator Dr. Robert Wild, professor of ob.gyn. and adjunct professor of medicine–cardiology at the center.

The nested case-control study examined the Women’s Health Initiative cohort for an effect modification between elevated baseline risk and hormone therapy (HT). It found 359 incident cases of coronary heart disease (CHD), and matched these to 817 controls without CHD. Controls were matched with a variety of criteria, including prevalent cardiovascular disease at baseline. Trials of estrogen plus progesterone and estrogen alone were analyzed separately and in a pooled analysis.

Metabolic syndrome was defined by ATP (Adult Treatment Panel) III criteria, where three of the following five criteria are met: elevated waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose.

In the pooled trial analysis of estrogen plus progesterone and estrogen alone, the metabolic syndrome was found to be an effect modifier. The odds ratio for treatment effect was 0.98 for women without the metabolic syndrome and 1.72 for those with the metabolic syndrome.

The individual trials had limited power, said Dr. Wild, but the findings were similar.

"Women without metabolic syndrome had no increase in risk of coronary heart disease vs. placebo, whereas women with metabolic syndrome had elevated risk," said Dr. Wild.

The reasons for this heightened risk might be more advanced stages of atherosclerosis and a heightened thrombogenic state among women with the metabolic syndrome, he said.

"Baseline CHD risk assessment may be helpful to identify women at increased risk for CHD when taking hormone therapy," said Dr. Wild.

Dr. Wild disclosed no significant financial relationships. This study was sponsored by the University of Oklahoma Health Sciences Center, Oklahoma City.

CHICAGO - Estrogen may safely and effectively be administered vaginally in a very low-dose 0.005% estriol gel to treat vaginal atrophy, said Dr. Concepcion Nieto of Italfarmaco S.A. of Madrid.

"The new estriol vaginal gel formulation, providing a very low amount of estriol per application [50 g], is highly efficacious in the improvement of the symptoms related to postmenopausal vaginal atrophy," she said at the annual meeting of the North American Menopause Society.

Dr. Nieto reported the results of a randomized, double-blind, placebo-controlled multicenter study of 167 women randomized 2:1 to the investigational estriol gel or placebo. She said that the gel provides 10 times less hormone per application than the European reference product, Ovestinon 0.1%, and that it is not approved by the Food and Drug Administration for use in the United States.

The 0.005% estriol vaginal gel was approved in Europe in July 2010 and will be proximately marketed in Europe under the brand names of Blissel and Gelistrol, Dr. Nieto said in a later interview.

Estriol is a metabolite of estradiol and estrone, but has lower estrogenic potency than estradiol. It also has a greater relative affinity for beta than for alpha estrogen receptors.

The study’s primary objective was to evaluate the efficacy of 0.005% estriol vaginal gel after 12 weeks of treatment. Safety was a secondary objective.

Postmenopausal amenorrheic women with signs and symptoms of vaginal atrophy made up the study population. Symptoms of vaginal atrophy included dryness, dyspareunia, pruritus, burning, and dysuria, and signs included dry vaginal mucosa, pallor, fragility, flattening of vaginal folds, and petechiae. Medication was administered daily in weeks 1-3 and twice weekly in weeks 4-12.

The primary efficacy variable was change in maturation value of vaginal epithelium from baseline to week 12. Symptoms were evaluated by change in global symptom score at baseline and at week 12.

The women in the study population (114 active, 53 placebo) averaged 56.7 years, had a mean body mass index of 26.0 kg/m2, and 9.8 years of menopause. All complained of vaginal dryness at baseline, more than 90% complained of dyspareunia, and more than half, of pruritus. The women also complained of burning and dysuria. The most bothersome symptom was vaginal dryness, in 59% of women.

The patients’ opinion of the treatment was largely favorable. In the active treatment group, 97 of 112 (87%) rated the treatment excellent, good, or acceptable, vs. 37 of 53 (70%) in the placebo group.

"The 0.005% estriol vaginal gel has proved to be significantly more efficacious than the placebo gel over the local symptomatology," said Dr. Nieto. "This effect is clinically relevant, as shown by the evaluation of the patients greatly in favor of estriol regarding the general efficacy of the treatment on finishing the study."

A physician in the audience said, "The FDA requires now an improvement in [the] most bothersome symptom, which you recorded. Was there a statistically significant reduction in [the] most bothersome symptom?"

"Yes," said Dr. Nieto. "We analyzed the most bothersome symptom, and we observed in vaginal dryness that at week 12, 88% of women had improved or were cured from the vaginal dryness, and 66% of women that received the placebo improved or were cured."

The study was sponsored by Italfarmaco SA, the Spanish affiliate of Grupo Italfarmaco, a pharmaceutical company operating in Europe and South America. Dr. Nieto is the medical director of Italfarmaco. No other member of the investigational team disclosed a financially relevant relationship.

CHICAGO - Estrogen may safely and effectively be administered vaginally in a very low-dose 0.005% estriol gel to treat vaginal atrophy, said Dr. Concepcion Nieto of Italfarmaco S.A. of Madrid.

"The new estriol vaginal gel formulation, providing a very low amount of estriol per application [50 g], is highly efficacious in the improvement of the symptoms related to postmenopausal vaginal atrophy," she said at the annual meeting of the North American Menopause Society.

Dr. Nieto reported the results of a randomized, double-blind, placebo-controlled multicenter study of 167 women randomized 2:1 to the investigational estriol gel or placebo. She said that the gel provides 10 times less hormone per application than the European reference product, Ovestinon 0.1%, and that it is not approved by the Food and Drug Administration for use in the United States.

The 0.005% estriol vaginal gel was approved in Europe in July 2010 and will be proximately marketed in Europe under the brand names of Blissel and Gelistrol, Dr. Nieto said in a later interview.

Estriol is a metabolite of estradiol and estrone, but has lower estrogenic potency than estradiol. It also has a greater relative affinity for beta than for alpha estrogen receptors.

The study’s primary objective was to evaluate the efficacy of 0.005% estriol vaginal gel after 12 weeks of treatment. Safety was a secondary objective.

Postmenopausal amenorrheic women with signs and symptoms of vaginal atrophy made up the study population. Symptoms of vaginal atrophy included dryness, dyspareunia, pruritus, burning, and dysuria, and signs included dry vaginal mucosa, pallor, fragility, flattening of vaginal folds, and petechiae. Medication was administered daily in weeks 1-3 and twice weekly in weeks 4-12.

The primary efficacy variable was change in maturation value of vaginal epithelium from baseline to week 12. Symptoms were evaluated by change in global symptom score at baseline and at week 12.

The women in the study population (114 active, 53 placebo) averaged 56.7 years, had a mean body mass index of 26.0 kg/m2, and 9.8 years of menopause. All complained of vaginal dryness at baseline, more than 90% complained of dyspareunia, and more than half, of pruritus. The women also complained of burning and dysuria. The most bothersome symptom was vaginal dryness, in 59% of women.

The patients’ opinion of the treatment was largely favorable. In the active treatment group, 97 of 112 (87%) rated the treatment excellent, good, or acceptable, vs. 37 of 53 (70%) in the placebo group.

"The 0.005% estriol vaginal gel has proved to be significantly more efficacious than the placebo gel over the local symptomatology," said Dr. Nieto. "This effect is clinically relevant, as shown by the evaluation of the patients greatly in favor of estriol regarding the general efficacy of the treatment on finishing the study."

A physician in the audience said, "The FDA requires now an improvement in [the] most bothersome symptom, which you recorded. Was there a statistically significant reduction in [the] most bothersome symptom?"

"Yes," said Dr. Nieto. "We analyzed the most bothersome symptom, and we observed in vaginal dryness that at week 12, 88% of women had improved or were cured from the vaginal dryness, and 66% of women that received the placebo improved or were cured."

The study was sponsored by Italfarmaco SA, the Spanish affiliate of Grupo Italfarmaco, a pharmaceutical company operating in Europe and South America. Dr. Nieto is the medical director of Italfarmaco. No other member of the investigational team disclosed a financially relevant relationship.

CHICAGO - Estrogen may safely and effectively be administered vaginally in a very low-dose 0.005% estriol gel to treat vaginal atrophy, said Dr. Concepcion Nieto of Italfarmaco S.A. of Madrid.

"The new estriol vaginal gel formulation, providing a very low amount of estriol per application [50 g], is highly efficacious in the improvement of the symptoms related to postmenopausal vaginal atrophy," she said at the annual meeting of the North American Menopause Society.

Dr. Nieto reported the results of a randomized, double-blind, placebo-controlled multicenter study of 167 women randomized 2:1 to the investigational estriol gel or placebo. She said that the gel provides 10 times less hormone per application than the European reference product, Ovestinon 0.1%, and that it is not approved by the Food and Drug Administration for use in the United States.

The 0.005% estriol vaginal gel was approved in Europe in July 2010 and will be proximately marketed in Europe under the brand names of Blissel and Gelistrol, Dr. Nieto said in a later interview.

Estriol is a metabolite of estradiol and estrone, but has lower estrogenic potency than estradiol. It also has a greater relative affinity for beta than for alpha estrogen receptors.

The study’s primary objective was to evaluate the efficacy of 0.005% estriol vaginal gel after 12 weeks of treatment. Safety was a secondary objective.

Postmenopausal amenorrheic women with signs and symptoms of vaginal atrophy made up the study population. Symptoms of vaginal atrophy included dryness, dyspareunia, pruritus, burning, and dysuria, and signs included dry vaginal mucosa, pallor, fragility, flattening of vaginal folds, and petechiae. Medication was administered daily in weeks 1-3 and twice weekly in weeks 4-12.

The primary efficacy variable was change in maturation value of vaginal epithelium from baseline to week 12. Symptoms were evaluated by change in global symptom score at baseline and at week 12.

The women in the study population (114 active, 53 placebo) averaged 56.7 years, had a mean body mass index of 26.0 kg/m2, and 9.8 years of menopause. All complained of vaginal dryness at baseline, more than 90% complained of dyspareunia, and more than half, of pruritus. The women also complained of burning and dysuria. The most bothersome symptom was vaginal dryness, in 59% of women.

The patients’ opinion of the treatment was largely favorable. In the active treatment group, 97 of 112 (87%) rated the treatment excellent, good, or acceptable, vs. 37 of 53 (70%) in the placebo group.

"The 0.005% estriol vaginal gel has proved to be significantly more efficacious than the placebo gel over the local symptomatology," said Dr. Nieto. "This effect is clinically relevant, as shown by the evaluation of the patients greatly in favor of estriol regarding the general efficacy of the treatment on finishing the study."

A physician in the audience said, "The FDA requires now an improvement in [the] most bothersome symptom, which you recorded. Was there a statistically significant reduction in [the] most bothersome symptom?"

"Yes," said Dr. Nieto. "We analyzed the most bothersome symptom, and we observed in vaginal dryness that at week 12, 88% of women had improved or were cured from the vaginal dryness, and 66% of women that received the placebo improved or were cured."

The study was sponsored by Italfarmaco SA, the Spanish affiliate of Grupo Italfarmaco, a pharmaceutical company operating in Europe and South America. Dr. Nieto is the medical director of Italfarmaco. No other member of the investigational team disclosed a financially relevant relationship.

CHICAGO – Prescriptions for hormone therapy for elderly postmenopausal women declined significantly after the results of the Women’s Health Initiative were reported in May 2002, and it now appears that there has been a correspondingly steep rise in hip fracture rates, said Roksana Karim, Ph.D., of the University of Southern California, Los Angeles.

"The rise in hip fracture rates in elderly postmenopausal women may be partially attributed to the continued decline in hormone therapy use," she said at the annual meeting of the North American Menopause Society. "Hormone therapy–related benefits on hip fracture do not carry over after cessation."

This was the conclusion of a longitudinal observational study of 80,995 postmenopausal women aged 60 years or older using data from 11 Kaiser Permanente medical centers in southern California. The study was designed to assess the risk of hip fracture for women who stopped taking hormone therapy (HT), compared with those who continued the therapy. It was also designed to evaluate the risk of hip fracture over time after stopping HT, and to measure bone mineral density (BMD) over time after stopping HT.

Data was collected on hip fracture, HT use, and the use of antiosteoporotic medication from June 2002 through December 2008. All hip fractures were verified by chart review by an orthopedic surgeon who was blinded to patients’ HT status. Exclusion criteria included fractures secondary to tumors or high-energy trauma, and periprosthetic fractures. Patients were considered to be HT users if they had filled at least two prescriptions in a given year, as each prescription provides a 3-month supply of medication. HT was defined as estrogen alone or estrogen plus progesterone.

BMD data of the hip and lumbar regions were available for 54,209 women (67%). The 80,955 women had a mean age of 68.8 years and a mean body mass index of 26.9 kg/m2; the study’s mean follow-up was 5.6 years. There were 1,419 hip fractures (2%) and 6,928 deaths (9%). In all, 15% of the 80,955 patients (12,486) were terminated from Kaiser.

Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustments for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture (hazard ratio, 1.55), said Dr. Karim. She also said that hip fracture risk significantly increased with 2 or more years of HT cessation. Mean BMD was significantly and inversely associated with cumulative years of HT nonuse, she said.

Dr. Karim acknowledged that the study was limited by lack of body mass index data in 47% of the population, or information on history of past HT use or on previous fractures.

The estimated annual cost for osteoporotic fractures in the United States is $18 billion, and hip fractures result in a greater cost and disability than do all other osteoporotic fractures combined, said Dr. Karim.

"Women at risk of hip fracture should consider carefully before making a decision of stopping using hormone therapy," she said.

During a question-and-answer session, Andrea LaCroix, Ph.D, professor of epidemiology at the University of Washington, Seattle, said, "It certainly comes as no surprise that women discontinue hormone therapy. There’s some loss of bone density and an increase in hip fracture rates. I agree with the conclusion that women coming off hormone therapy should be counseled about their potential for losing bone and having an increased fracture risk, but they’ve never enjoyed more alternatives for the prevention of hip fracture than they do today, including many agents besides hormone therapy."

Dr. Karim said she had no financial conflicts of interest. The study was supported by the University of Southern California.

CHICAGO – Prescriptions for hormone therapy for elderly postmenopausal women declined significantly after the results of the Women’s Health Initiative were reported in May 2002, and it now appears that there has been a correspondingly steep rise in hip fracture rates, said Roksana Karim, Ph.D., of the University of Southern California, Los Angeles.

"The rise in hip fracture rates in elderly postmenopausal women may be partially attributed to the continued decline in hormone therapy use," she said at the annual meeting of the North American Menopause Society. "Hormone therapy–related benefits on hip fracture do not carry over after cessation."

This was the conclusion of a longitudinal observational study of 80,995 postmenopausal women aged 60 years or older using data from 11 Kaiser Permanente medical centers in southern California. The study was designed to assess the risk of hip fracture for women who stopped taking hormone therapy (HT), compared with those who continued the therapy. It was also designed to evaluate the risk of hip fracture over time after stopping HT, and to measure bone mineral density (BMD) over time after stopping HT.

Data was collected on hip fracture, HT use, and the use of antiosteoporotic medication from June 2002 through December 2008. All hip fractures were verified by chart review by an orthopedic surgeon who was blinded to patients’ HT status. Exclusion criteria included fractures secondary to tumors or high-energy trauma, and periprosthetic fractures. Patients were considered to be HT users if they had filled at least two prescriptions in a given year, as each prescription provides a 3-month supply of medication. HT was defined as estrogen alone or estrogen plus progesterone.

BMD data of the hip and lumbar regions were available for 54,209 women (67%). The 80,955 women had a mean age of 68.8 years and a mean body mass index of 26.9 kg/m2; the study’s mean follow-up was 5.6 years. There were 1,419 hip fractures (2%) and 6,928 deaths (9%). In all, 15% of the 80,955 patients (12,486) were terminated from Kaiser.

Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustments for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture (hazard ratio, 1.55), said Dr. Karim. She also said that hip fracture risk significantly increased with 2 or more years of HT cessation. Mean BMD was significantly and inversely associated with cumulative years of HT nonuse, she said.

Dr. Karim acknowledged that the study was limited by lack of body mass index data in 47% of the population, or information on history of past HT use or on previous fractures.

The estimated annual cost for osteoporotic fractures in the United States is $18 billion, and hip fractures result in a greater cost and disability than do all other osteoporotic fractures combined, said Dr. Karim.

"Women at risk of hip fracture should consider carefully before making a decision of stopping using hormone therapy," she said.

During a question-and-answer session, Andrea LaCroix, Ph.D, professor of epidemiology at the University of Washington, Seattle, said, "It certainly comes as no surprise that women discontinue hormone therapy. There’s some loss of bone density and an increase in hip fracture rates. I agree with the conclusion that women coming off hormone therapy should be counseled about their potential for losing bone and having an increased fracture risk, but they’ve never enjoyed more alternatives for the prevention of hip fracture than they do today, including many agents besides hormone therapy."

Dr. Karim said she had no financial conflicts of interest. The study was supported by the University of Southern California.

CHICAGO – Prescriptions for hormone therapy for elderly postmenopausal women declined significantly after the results of the Women’s Health Initiative were reported in May 2002, and it now appears that there has been a correspondingly steep rise in hip fracture rates, said Roksana Karim, Ph.D., of the University of Southern California, Los Angeles.

"The rise in hip fracture rates in elderly postmenopausal women may be partially attributed to the continued decline in hormone therapy use," she said at the annual meeting of the North American Menopause Society. "Hormone therapy–related benefits on hip fracture do not carry over after cessation."

This was the conclusion of a longitudinal observational study of 80,995 postmenopausal women aged 60 years or older using data from 11 Kaiser Permanente medical centers in southern California. The study was designed to assess the risk of hip fracture for women who stopped taking hormone therapy (HT), compared with those who continued the therapy. It was also designed to evaluate the risk of hip fracture over time after stopping HT, and to measure bone mineral density (BMD) over time after stopping HT.

Data was collected on hip fracture, HT use, and the use of antiosteoporotic medication from June 2002 through December 2008. All hip fractures were verified by chart review by an orthopedic surgeon who was blinded to patients’ HT status. Exclusion criteria included fractures secondary to tumors or high-energy trauma, and periprosthetic fractures. Patients were considered to be HT users if they had filled at least two prescriptions in a given year, as each prescription provides a 3-month supply of medication. HT was defined as estrogen alone or estrogen plus progesterone.

BMD data of the hip and lumbar regions were available for 54,209 women (67%). The 80,955 women had a mean age of 68.8 years and a mean body mass index of 26.9 kg/m2; the study’s mean follow-up was 5.6 years. There were 1,419 hip fractures (2%) and 6,928 deaths (9%). In all, 15% of the 80,955 patients (12,486) were terminated from Kaiser.

Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustments for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture (hazard ratio, 1.55), said Dr. Karim. She also said that hip fracture risk significantly increased with 2 or more years of HT cessation. Mean BMD was significantly and inversely associated with cumulative years of HT nonuse, she said.

Dr. Karim acknowledged that the study was limited by lack of body mass index data in 47% of the population, or information on history of past HT use or on previous fractures.

The estimated annual cost for osteoporotic fractures in the United States is $18 billion, and hip fractures result in a greater cost and disability than do all other osteoporotic fractures combined, said Dr. Karim.

"Women at risk of hip fracture should consider carefully before making a decision of stopping using hormone therapy," she said.

During a question-and-answer session, Andrea LaCroix, Ph.D, professor of epidemiology at the University of Washington, Seattle, said, "It certainly comes as no surprise that women discontinue hormone therapy. There’s some loss of bone density and an increase in hip fracture rates. I agree with the conclusion that women coming off hormone therapy should be counseled about their potential for losing bone and having an increased fracture risk, but they’ve never enjoyed more alternatives for the prevention of hip fracture than they do today, including many agents besides hormone therapy."

Dr. Karim said she had no financial conflicts of interest. The study was supported by the University of Southern California.

Major Finding: Radiological Evaluation and Breast Density (READ) trial analysis predicts 2 months of disturbed sleep after stopping hormone therapy.

Data Source: Sample size of 1,405 from the READ trial database randomized to three arms: HT (518), 1-month cessation (452), 2-month cessation (435).

Disclosures: None reported. The trial was sponsored by the Department of Defense, the National Institute on Aging, and the nonprofit Group Health Research Institute.

CHICAGO — Almost 40% of women report sleep problems in midlife, and since hormone therapy benefits sleep, cessation of that therapy might have the opposite effect. A study of 1,704 women from the Group Health Research Institute of Seattle confirms that it does.

“Sleep problems were related to the suspension of hormone therapy for 1 or 2 months,” investigator Sarah E. Tom, Ph.D., formerly of the institute, said of the study's findings.

“Women who are discontinuing hormone therapy may benefit from alternative sleep management strategies immediately following discontinuation,” she said.

This was a secondary analysis of data from the READ (Radiological Evaluation and Breast Density) study, a trial designed to test whether short-term suspension of hormone therapy resulted in better screening mammography performance. The trial recruited women aged 45-80 years from Group Health, a nonprofit health care system based in Washington state. The recruits were due for a screening mammography, and reported on use of hormone therapy for 2 years. They were randomized to continue hormone therapy or to suspend it for either 1 or 2 months prior to mammography.

The survey used a questionnaire that asked about the number of days subjects had sleep complaints, including trouble falling asleep and waking while sleeping.

Various confounding variables, including alcohol consumption, body mass index, age, race, and ethnicity, were considered, Dr. Tom said.

Of the 1,704 women, 1,405 had complete information on all variables. Of this group, 518 were randomized to continue hormone therapy, 452 to suspend therapy for 1 month, and 435 to suspend it for 2 months.

Demographic profiles were similar across all randomization groups. In the group continuing hormone therapy, for example, more than 90% were white, and more than 50% used estrogen only. Sleep problems were comparable in the groups suspending therapy for 1 month or 2 months.

The group randomized to a 2-month suspension, had an increase of about 0.7 days wi trouble with their sleep, comparedto with women who continued therapy, Dr. Tom said. Waking while sleeping wasofrequently reported pand about 35% of women in the two hormone cessation groups reported using sleep aids in the previous week.

The study concluded that sleep problems were related to suspension of hormone therapy for 1 or 2 months. Differences were modest but persistent across sleep items, and were similar for the 1- and 2-month suspension groups.

Major Finding: Radiological Evaluation and Breast Density (READ) trial analysis predicts 2 months of disturbed sleep after stopping hormone therapy.

Data Source: Sample size of 1,405 from the READ trial database randomized to three arms: HT (518), 1-month cessation (452), 2-month cessation (435).

Disclosures: None reported. The trial was sponsored by the Department of Defense, the National Institute on Aging, and the nonprofit Group Health Research Institute.

CHICAGO — Almost 40% of women report sleep problems in midlife, and since hormone therapy benefits sleep, cessation of that therapy might have the opposite effect. A study of 1,704 women from the Group Health Research Institute of Seattle confirms that it does.

“Sleep problems were related to the suspension of hormone therapy for 1 or 2 months,” investigator Sarah E. Tom, Ph.D., formerly of the institute, said of the study's findings.

“Women who are discontinuing hormone therapy may benefit from alternative sleep management strategies immediately following discontinuation,” she said.

This was a secondary analysis of data from the READ (Radiological Evaluation and Breast Density) study, a trial designed to test whether short-term suspension of hormone therapy resulted in better screening mammography performance. The trial recruited women aged 45-80 years from Group Health, a nonprofit health care system based in Washington state. The recruits were due for a screening mammography, and reported on use of hormone therapy for 2 years. They were randomized to continue hormone therapy or to suspend it for either 1 or 2 months prior to mammography.

The survey used a questionnaire that asked about the number of days subjects had sleep complaints, including trouble falling asleep and waking while sleeping.

Various confounding variables, including alcohol consumption, body mass index, age, race, and ethnicity, were considered, Dr. Tom said.

Of the 1,704 women, 1,405 had complete information on all variables. Of this group, 518 were randomized to continue hormone therapy, 452 to suspend therapy for 1 month, and 435 to suspend it for 2 months.

Demographic profiles were similar across all randomization groups. In the group continuing hormone therapy, for example, more than 90% were white, and more than 50% used estrogen only. Sleep problems were comparable in the groups suspending therapy for 1 month or 2 months.

The group randomized to a 2-month suspension, had an increase of about 0.7 days wi trouble with their sleep, comparedto with women who continued therapy, Dr. Tom said. Waking while sleeping wasofrequently reported pand about 35% of women in the two hormone cessation groups reported using sleep aids in the previous week.

The study concluded that sleep problems were related to suspension of hormone therapy for 1 or 2 months. Differences were modest but persistent across sleep items, and were similar for the 1- and 2-month suspension groups.

Major Finding: Radiological Evaluation and Breast Density (READ) trial analysis predicts 2 months of disturbed sleep after stopping hormone therapy.

Data Source: Sample size of 1,405 from the READ trial database randomized to three arms: HT (518), 1-month cessation (452), 2-month cessation (435).

Disclosures: None reported. The trial was sponsored by the Department of Defense, the National Institute on Aging, and the nonprofit Group Health Research Institute.

CHICAGO — Almost 40% of women report sleep problems in midlife, and since hormone therapy benefits sleep, cessation of that therapy might have the opposite effect. A study of 1,704 women from the Group Health Research Institute of Seattle confirms that it does.

“Sleep problems were related to the suspension of hormone therapy for 1 or 2 months,” investigator Sarah E. Tom, Ph.D., formerly of the institute, said of the study's findings.

“Women who are discontinuing hormone therapy may benefit from alternative sleep management strategies immediately following discontinuation,” she said.

This was a secondary analysis of data from the READ (Radiological Evaluation and Breast Density) study, a trial designed to test whether short-term suspension of hormone therapy resulted in better screening mammography performance. The trial recruited women aged 45-80 years from Group Health, a nonprofit health care system based in Washington state. The recruits were due for a screening mammography, and reported on use of hormone therapy for 2 years. They were randomized to continue hormone therapy or to suspend it for either 1 or 2 months prior to mammography.

The survey used a questionnaire that asked about the number of days subjects had sleep complaints, including trouble falling asleep and waking while sleeping.

Various confounding variables, including alcohol consumption, body mass index, age, race, and ethnicity, were considered, Dr. Tom said.

Of the 1,704 women, 1,405 had complete information on all variables. Of this group, 518 were randomized to continue hormone therapy, 452 to suspend therapy for 1 month, and 435 to suspend it for 2 months.

Demographic profiles were similar across all randomization groups. In the group continuing hormone therapy, for example, more than 90% were white, and more than 50% used estrogen only. Sleep problems were comparable in the groups suspending therapy for 1 month or 2 months.

The group randomized to a 2-month suspension, had an increase of about 0.7 days wi trouble with their sleep, comparedto with women who continued therapy, Dr. Tom said. Waking while sleeping wasofrequently reported pand about 35% of women in the two hormone cessation groups reported using sleep aids in the previous week.

The study concluded that sleep problems were related to suspension of hormone therapy for 1 or 2 months. Differences were modest but persistent across sleep items, and were similar for the 1- and 2-month suspension groups.

CHICAGO — The risk for cancer in children taking a biologic agent for management of juvenile idiopathic arthritis appears to be small, Dr. Daniel J. Lovell said.

Parents ask: “Is this therapy going to increase my child's risk for cancer?” said Dr. Lovell, a pediatric rheumatologist at the Cincinnati Children's Hospital Medical Center. To answer that question, one must determine:

1. the risk for cancer in the healthy pediatric population;

2. whether the cancer risk is increased in those who develop JIA;

3. whether the risk is increased by nonbiologic therapies for JIA; and

4. whether exposure to biologic therapy raises the risk.

We have an accurate answer to No. 1, but the accurate answer to No. 4 requires that we also have answers to Nos. 2 and 3, which we do not at this time, Dr. Lovell said.

The arthritis in children with persistent oligoarticular JIA can often be successfully treated only with intra-articular corticosteroids. However, the risk for uveitis is highest in this subtype of JIA. The uveitis of JIA is a chronic, nongranulomatous inflammation of the anterior uveal tract of the eye, and is asymptomatic in up to 80% of children. In 70% of the cases, both eyes will be involved within 1 year.

Although the proper initial treatment of JIA-associated uveitis is topical corticosteroid eye drops, Dr. Lovell suggested that if the need for ongoing topical therapy persists beyond 3 months, then there may need to be systemic anti-inflammatory treatment for the uveitis, even though this might alarm an ophthalmologist. Complications of topical or local corticosteroid therapy in the eyes include cataract, glaucoma, and band keratopathy.

With systemic JIA, which is thought by many to be an autoinflammatory disease rather than an autoimmune disease, the logical therapeutic choices are biologics that specifically block either interleukin (IL)-1 or IL-6, because they are the cytokines most directly involved in the disease's pathophysiology.

Some children with systemic JIA demonstrate a rapid and dramatic response to treatment with the IL-1 receptor antagonist anakinra, but some do not respond, and in some the benefit wanes with ongoing treatment (Ann. Rheum. Dis. 2008;67:302–8).

Results of treatment of systemic JIA with the IL-6 inhibitor tocilizumab have been very promising. Patients treated with this biologic often start to show improvement in systemic features within hours, and their arthritis was also greatly improved (Lancet 2008;371:998–1006).

On the subject of medications, including biologics, used to treat children with JIA, it is critical to calculate the dose on the basis of milligrams per kilogram or body surface area. “That really causes you to think about your medical math,” said Dr. Lovell. He gave the example of a 6-year-old child, height 4 feet 11 inches, weight 55 lb, whose dosages for common JIA treatments according to the published pediatric recommendations, which are based on weight or surface area, were very similar to adult doses. It is a common problem for adult rheumatologists who treat JIA patients to use the right drugs but in amounts below the efficacious dose because of concern about giving a child adult-sized dosages.

“My advice to you is look at the dosage based on milligrams per kilogram or milligrams per meter squared, do your math, gird your loins, and write the prescription. If you're going to use the agent, you have to do it in the proper dose in the kids to get the proper effect.”

In the polyarticular forms of JIA, where more than five joints are involved, the most common treatment approach is methotrexate.

“Methotrexate is our most studied agent ever in terms of kids with arthritis,” said Dr. Lovell. However, many children with polyarticular forms of JIA do not respond to or tolerate methotrexate. It is in these children that the anti–tumor necrosis factor (anti-TNF) biologics have shown dramatic benefit.

The question of whether biologics increase a child's risk for cancer is actually several linked questions, said Dr. Lovell. These include the child's background risk, independent of arthritis; the risk from just having JIA (which is unknown); the risk from prior treatments for JIA such as methotrexate and steroids; and the potential risk from taking biologics.

Dr. Lovell has developed his own unofficial estimate of risk, limited to etanercept, because that's where the best JIA-related data are found. The observed frequency of cancer in children with JIA treated with etanercept based on FDA data is six cases in 9,200 patients or one case per 1,533 children. Epidemiologic data for the overall incidence of cancer in American children under the age of 15 years are one case per 7,252 children. Accordingly, the relative risk compared with the healthy pediatric population is 4.7 – with many caveats, he says.

“Fortunately, this still means that cancer in children with JIA treated with etanercept is very uncommon – about one case of cancer in every 1,500 children with JIA treated with etanercept.” In other words, relatively modest.

Dominick Co of Children's Hospital of Wisconsin, Milwaukee, said, “We have a number of very difficult poly-JIA patients who seem to have an initial response to some of the biologics and then after several months will not respond, and we'll switch them. Have you had a similar experience with cycling through biologics?”

Dr. Lovell responded that he saw poly-JIA patients treated with biologics “where there was an initial excellent response and then a secondary loss of response. We went back to the families and the patients and discussed the situation with them. In about half of the patients (usually adolescents), that loss of response was due to the patient developing poor compliance with taking the biologic since they felt so well. In other cases the loss of response was more difficult to understand, but it certainly occurs and we have dealt with it by either increasing the dose of the biologic or changing to another biologic.”

Dr. Lovell disclosed consulting fees or other remuneration from Centocor, Amgen, Abbott, Pfizer, Regeneron, Hoffman-La Roche, Novartis, UBC, Xoma, and Wyeth.

CHICAGO — The risk for cancer in children taking a biologic agent for management of juvenile idiopathic arthritis appears to be small, Dr. Daniel J. Lovell said.

Parents ask: “Is this therapy going to increase my child's risk for cancer?” said Dr. Lovell, a pediatric rheumatologist at the Cincinnati Children's Hospital Medical Center. To answer that question, one must determine:

1. the risk for cancer in the healthy pediatric population;

2. whether the cancer risk is increased in those who develop JIA;

3. whether the risk is increased by nonbiologic therapies for JIA; and

4. whether exposure to biologic therapy raises the risk.

We have an accurate answer to No. 1, but the accurate answer to No. 4 requires that we also have answers to Nos. 2 and 3, which we do not at this time, Dr. Lovell said.

The arthritis in children with persistent oligoarticular JIA can often be successfully treated only with intra-articular corticosteroids. However, the risk for uveitis is highest in this subtype of JIA. The uveitis of JIA is a chronic, nongranulomatous inflammation of the anterior uveal tract of the eye, and is asymptomatic in up to 80% of children. In 70% of the cases, both eyes will be involved within 1 year.

Although the proper initial treatment of JIA-associated uveitis is topical corticosteroid eye drops, Dr. Lovell suggested that if the need for ongoing topical therapy persists beyond 3 months, then there may need to be systemic anti-inflammatory treatment for the uveitis, even though this might alarm an ophthalmologist. Complications of topical or local corticosteroid therapy in the eyes include cataract, glaucoma, and band keratopathy.

With systemic JIA, which is thought by many to be an autoinflammatory disease rather than an autoimmune disease, the logical therapeutic choices are biologics that specifically block either interleukin (IL)-1 or IL-6, because they are the cytokines most directly involved in the disease's pathophysiology.

Some children with systemic JIA demonstrate a rapid and dramatic response to treatment with the IL-1 receptor antagonist anakinra, but some do not respond, and in some the benefit wanes with ongoing treatment (Ann. Rheum. Dis. 2008;67:302–8).

Results of treatment of systemic JIA with the IL-6 inhibitor tocilizumab have been very promising. Patients treated with this biologic often start to show improvement in systemic features within hours, and their arthritis was also greatly improved (Lancet 2008;371:998–1006).

On the subject of medications, including biologics, used to treat children with JIA, it is critical to calculate the dose on the basis of milligrams per kilogram or body surface area. “That really causes you to think about your medical math,” said Dr. Lovell. He gave the example of a 6-year-old child, height 4 feet 11 inches, weight 55 lb, whose dosages for common JIA treatments according to the published pediatric recommendations, which are based on weight or surface area, were very similar to adult doses. It is a common problem for adult rheumatologists who treat JIA patients to use the right drugs but in amounts below the efficacious dose because of concern about giving a child adult-sized dosages.

“My advice to you is look at the dosage based on milligrams per kilogram or milligrams per meter squared, do your math, gird your loins, and write the prescription. If you're going to use the agent, you have to do it in the proper dose in the kids to get the proper effect.”

In the polyarticular forms of JIA, where more than five joints are involved, the most common treatment approach is methotrexate.

“Methotrexate is our most studied agent ever in terms of kids with arthritis,” said Dr. Lovell. However, many children with polyarticular forms of JIA do not respond to or tolerate methotrexate. It is in these children that the anti–tumor necrosis factor (anti-TNF) biologics have shown dramatic benefit.

The question of whether biologics increase a child's risk for cancer is actually several linked questions, said Dr. Lovell. These include the child's background risk, independent of arthritis; the risk from just having JIA (which is unknown); the risk from prior treatments for JIA such as methotrexate and steroids; and the potential risk from taking biologics.

Dr. Lovell has developed his own unofficial estimate of risk, limited to etanercept, because that's where the best JIA-related data are found. The observed frequency of cancer in children with JIA treated with etanercept based on FDA data is six cases in 9,200 patients or one case per 1,533 children. Epidemiologic data for the overall incidence of cancer in American children under the age of 15 years are one case per 7,252 children. Accordingly, the relative risk compared with the healthy pediatric population is 4.7 – with many caveats, he says.

“Fortunately, this still means that cancer in children with JIA treated with etanercept is very uncommon – about one case of cancer in every 1,500 children with JIA treated with etanercept.” In other words, relatively modest.

Dominick Co of Children's Hospital of Wisconsin, Milwaukee, said, “We have a number of very difficult poly-JIA patients who seem to have an initial response to some of the biologics and then after several months will not respond, and we'll switch them. Have you had a similar experience with cycling through biologics?”

Dr. Lovell responded that he saw poly-JIA patients treated with biologics “where there was an initial excellent response and then a secondary loss of response. We went back to the families and the patients and discussed the situation with them. In about half of the patients (usually adolescents), that loss of response was due to the patient developing poor compliance with taking the biologic since they felt so well. In other cases the loss of response was more difficult to understand, but it certainly occurs and we have dealt with it by either increasing the dose of the biologic or changing to another biologic.”

Dr. Lovell disclosed consulting fees or other remuneration from Centocor, Amgen, Abbott, Pfizer, Regeneron, Hoffman-La Roche, Novartis, UBC, Xoma, and Wyeth.

CHICAGO — The risk for cancer in children taking a biologic agent for management of juvenile idiopathic arthritis appears to be small, Dr. Daniel J. Lovell said.

Parents ask: “Is this therapy going to increase my child's risk for cancer?” said Dr. Lovell, a pediatric rheumatologist at the Cincinnati Children's Hospital Medical Center. To answer that question, one must determine:

1. the risk for cancer in the healthy pediatric population;

2. whether the cancer risk is increased in those who develop JIA;

3. whether the risk is increased by nonbiologic therapies for JIA; and

4. whether exposure to biologic therapy raises the risk.

We have an accurate answer to No. 1, but the accurate answer to No. 4 requires that we also have answers to Nos. 2 and 3, which we do not at this time, Dr. Lovell said.

The arthritis in children with persistent oligoarticular JIA can often be successfully treated only with intra-articular corticosteroids. However, the risk for uveitis is highest in this subtype of JIA. The uveitis of JIA is a chronic, nongranulomatous inflammation of the anterior uveal tract of the eye, and is asymptomatic in up to 80% of children. In 70% of the cases, both eyes will be involved within 1 year.

Although the proper initial treatment of JIA-associated uveitis is topical corticosteroid eye drops, Dr. Lovell suggested that if the need for ongoing topical therapy persists beyond 3 months, then there may need to be systemic anti-inflammatory treatment for the uveitis, even though this might alarm an ophthalmologist. Complications of topical or local corticosteroid therapy in the eyes include cataract, glaucoma, and band keratopathy.

With systemic JIA, which is thought by many to be an autoinflammatory disease rather than an autoimmune disease, the logical therapeutic choices are biologics that specifically block either interleukin (IL)-1 or IL-6, because they are the cytokines most directly involved in the disease's pathophysiology.

Some children with systemic JIA demonstrate a rapid and dramatic response to treatment with the IL-1 receptor antagonist anakinra, but some do not respond, and in some the benefit wanes with ongoing treatment (Ann. Rheum. Dis. 2008;67:302–8).

Results of treatment of systemic JIA with the IL-6 inhibitor tocilizumab have been very promising. Patients treated with this biologic often start to show improvement in systemic features within hours, and their arthritis was also greatly improved (Lancet 2008;371:998–1006).

On the subject of medications, including biologics, used to treat children with JIA, it is critical to calculate the dose on the basis of milligrams per kilogram or body surface area. “That really causes you to think about your medical math,” said Dr. Lovell. He gave the example of a 6-year-old child, height 4 feet 11 inches, weight 55 lb, whose dosages for common JIA treatments according to the published pediatric recommendations, which are based on weight or surface area, were very similar to adult doses. It is a common problem for adult rheumatologists who treat JIA patients to use the right drugs but in amounts below the efficacious dose because of concern about giving a child adult-sized dosages.

“My advice to you is look at the dosage based on milligrams per kilogram or milligrams per meter squared, do your math, gird your loins, and write the prescription. If you're going to use the agent, you have to do it in the proper dose in the kids to get the proper effect.”

In the polyarticular forms of JIA, where more than five joints are involved, the most common treatment approach is methotrexate.

“Methotrexate is our most studied agent ever in terms of kids with arthritis,” said Dr. Lovell. However, many children with polyarticular forms of JIA do not respond to or tolerate methotrexate. It is in these children that the anti–tumor necrosis factor (anti-TNF) biologics have shown dramatic benefit.

The question of whether biologics increase a child's risk for cancer is actually several linked questions, said Dr. Lovell. These include the child's background risk, independent of arthritis; the risk from just having JIA (which is unknown); the risk from prior treatments for JIA such as methotrexate and steroids; and the potential risk from taking biologics.

Dr. Lovell has developed his own unofficial estimate of risk, limited to etanercept, because that's where the best JIA-related data are found. The observed frequency of cancer in children with JIA treated with etanercept based on FDA data is six cases in 9,200 patients or one case per 1,533 children. Epidemiologic data for the overall incidence of cancer in American children under the age of 15 years are one case per 7,252 children. Accordingly, the relative risk compared with the healthy pediatric population is 4.7 – with many caveats, he says.

“Fortunately, this still means that cancer in children with JIA treated with etanercept is very uncommon – about one case of cancer in every 1,500 children with JIA treated with etanercept.” In other words, relatively modest.

Dominick Co of Children's Hospital of Wisconsin, Milwaukee, said, “We have a number of very difficult poly-JIA patients who seem to have an initial response to some of the biologics and then after several months will not respond, and we'll switch them. Have you had a similar experience with cycling through biologics?”

Dr. Lovell responded that he saw poly-JIA patients treated with biologics “where there was an initial excellent response and then a secondary loss of response. We went back to the families and the patients and discussed the situation with them. In about half of the patients (usually adolescents), that loss of response was due to the patient developing poor compliance with taking the biologic since they felt so well. In other cases the loss of response was more difficult to understand, but it certainly occurs and we have dealt with it by either increasing the dose of the biologic or changing to another biologic.”

Dr. Lovell disclosed consulting fees or other remuneration from Centocor, Amgen, Abbott, Pfizer, Regeneron, Hoffman-La Roche, Novartis, UBC, Xoma, and Wyeth.

CHICAGO – An extended-release formulation of gabapentin for hot flashes showed the potential both to minimize peak adverse events and to allow for less frequent dosing in a randomized, controlled trial of 565 women, said Dr. Wulf Utian.

"The results of the Breeze 2 study suggest that gabapentin–extended release 1,800 mg/day may be effective and well tolerated for the treatment of moderate to severe hot flashes in postmenopausal women," he noted at the annual meeting of the North American Menopause Society.

Gabapentin-ER releases over 8 hours, potentially minimizing peak adverse events and allowing once daily or twice daily dosing, said Dr. Utian, the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology at Case Western Reserve University in Cleveland. Gabapentin (Neurontin) is a novel anticonvulsant.

Breeze 2 is a prospective, multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women aged 18-70 years at 45 sites across the United States. The study had two active arms: gabapentin-ER 1,200 mg given once daily, and 1,800 mg given as 600 mg in the morning and 1,200 in the evening. Efficacy was assessed at 4 and 12 weeks, and the treatment duration was 3 months. The primary efficacy end points were reductions in the mean frequency of moderate to severe hot flashes and the average severity of hot flashes.

The trial’s secondary end points were the proportion of patients who were categorized as "much improved" or "very much improved" at 12 weeks in the self-reported Patient Global Impression of Change scale. Investigators also recorded their impression of the results of the therapy using the Clinician Global Impression of Change scale.

Postmenopausal women who had been experiencing seven or more moderate to severe hot flashes per day (or at least 50 per week), accompanied by sweating during at least the previous 30 days, were the trial population.

Baseline characteristics were similar across the three groups. In the 1,800-mg group, for example, the average age was 54 years, the women were 71% white, and the average body mass index was less than 30 kg/m2.

Data were subjected to both parametric and nonparametric analysis, said Dr. Utian, because parametric analyses can be influenced by outliers.

At 4 weeks and 12 weeks, change in the mean severity of moderate and severe hot flashes was –0.6 and –0.8 for 1,800-mg group vs. placebo. Change in frequency of these hot flashes was at the same statistical level at both time points for both dosing groups.

More than 60% of patients in both groups and more than 40% in the placebo group self-reported and were clinician reported as "very much improved" at 12 weeks. "This was a particularly high placebo response," said Dr. Utian.

Nonparametric analysis revealed a statistically significant change in median frequency of moderate to severe hot flashes at 4 weeks and 12 weeks in both active groups, compared with the placebo group.

Dizziness was the most commonly reported adverse event in both the 1,800-mg and 1,200-mg groups, whereas headache was most commonly reported in the placebo group. Somnolence was the second most common complaint in the active treatment groups. A total of 48 patients across both active treatment groups discontinued because of adverse events.

"Essentially, this long-release product was well tolerated, adverse events were mild, the difference was a slight difference in dizziness and somnolence during the titration, and [there was] no real difference in the adverse events" between the 1,800-mg and the 1,200-mg dosing regimens, said Dr. Utian. "The incidence of the adverse events declined markedly after 2-4 weeks of study therapy," he added.

Dr. Utian is a clinical consultant to Depomed Inc., the sponsor of the study. Some of the study investigators are Depomed employees.

CHICAGO – An extended-release formulation of gabapentin for hot flashes showed the potential both to minimize peak adverse events and to allow for less frequent dosing in a randomized, controlled trial of 565 women, said Dr. Wulf Utian.

"The results of the Breeze 2 study suggest that gabapentin–extended release 1,800 mg/day may be effective and well tolerated for the treatment of moderate to severe hot flashes in postmenopausal women," he noted at the annual meeting of the North American Menopause Society.

Gabapentin-ER releases over 8 hours, potentially minimizing peak adverse events and allowing once daily or twice daily dosing, said Dr. Utian, the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology at Case Western Reserve University in Cleveland. Gabapentin (Neurontin) is a novel anticonvulsant.

Breeze 2 is a prospective, multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women aged 18-70 years at 45 sites across the United States. The study had two active arms: gabapentin-ER 1,200 mg given once daily, and 1,800 mg given as 600 mg in the morning and 1,200 in the evening. Efficacy was assessed at 4 and 12 weeks, and the treatment duration was 3 months. The primary efficacy end points were reductions in the mean frequency of moderate to severe hot flashes and the average severity of hot flashes.

The trial’s secondary end points were the proportion of patients who were categorized as "much improved" or "very much improved" at 12 weeks in the self-reported Patient Global Impression of Change scale. Investigators also recorded their impression of the results of the therapy using the Clinician Global Impression of Change scale.

Postmenopausal women who had been experiencing seven or more moderate to severe hot flashes per day (or at least 50 per week), accompanied by sweating during at least the previous 30 days, were the trial population.

Baseline characteristics were similar across the three groups. In the 1,800-mg group, for example, the average age was 54 years, the women were 71% white, and the average body mass index was less than 30 kg/m2.

Data were subjected to both parametric and nonparametric analysis, said Dr. Utian, because parametric analyses can be influenced by outliers.

At 4 weeks and 12 weeks, change in the mean severity of moderate and severe hot flashes was –0.6 and –0.8 for 1,800-mg group vs. placebo. Change in frequency of these hot flashes was at the same statistical level at both time points for both dosing groups.

More than 60% of patients in both groups and more than 40% in the placebo group self-reported and were clinician reported as "very much improved" at 12 weeks. "This was a particularly high placebo response," said Dr. Utian.

Nonparametric analysis revealed a statistically significant change in median frequency of moderate to severe hot flashes at 4 weeks and 12 weeks in both active groups, compared with the placebo group.

Dizziness was the most commonly reported adverse event in both the 1,800-mg and 1,200-mg groups, whereas headache was most commonly reported in the placebo group. Somnolence was the second most common complaint in the active treatment groups. A total of 48 patients across both active treatment groups discontinued because of adverse events.

"Essentially, this long-release product was well tolerated, adverse events were mild, the difference was a slight difference in dizziness and somnolence during the titration, and [there was] no real difference in the adverse events" between the 1,800-mg and the 1,200-mg dosing regimens, said Dr. Utian. "The incidence of the adverse events declined markedly after 2-4 weeks of study therapy," he added.

Dr. Utian is a clinical consultant to Depomed Inc., the sponsor of the study. Some of the study investigators are Depomed employees.

CHICAGO – An extended-release formulation of gabapentin for hot flashes showed the potential both to minimize peak adverse events and to allow for less frequent dosing in a randomized, controlled trial of 565 women, said Dr. Wulf Utian.

"The results of the Breeze 2 study suggest that gabapentin–extended release 1,800 mg/day may be effective and well tolerated for the treatment of moderate to severe hot flashes in postmenopausal women," he noted at the annual meeting of the North American Menopause Society.

Gabapentin-ER releases over 8 hours, potentially minimizing peak adverse events and allowing once daily or twice daily dosing, said Dr. Utian, the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology at Case Western Reserve University in Cleveland. Gabapentin (Neurontin) is a novel anticonvulsant.

Breeze 2 is a prospective, multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women aged 18-70 years at 45 sites across the United States. The study had two active arms: gabapentin-ER 1,200 mg given once daily, and 1,800 mg given as 600 mg in the morning and 1,200 in the evening. Efficacy was assessed at 4 and 12 weeks, and the treatment duration was 3 months. The primary efficacy end points were reductions in the mean frequency of moderate to severe hot flashes and the average severity of hot flashes.

The trial’s secondary end points were the proportion of patients who were categorized as "much improved" or "very much improved" at 12 weeks in the self-reported Patient Global Impression of Change scale. Investigators also recorded their impression of the results of the therapy using the Clinician Global Impression of Change scale.

Postmenopausal women who had been experiencing seven or more moderate to severe hot flashes per day (or at least 50 per week), accompanied by sweating during at least the previous 30 days, were the trial population.

Baseline characteristics were similar across the three groups. In the 1,800-mg group, for example, the average age was 54 years, the women were 71% white, and the average body mass index was less than 30 kg/m2.

Data were subjected to both parametric and nonparametric analysis, said Dr. Utian, because parametric analyses can be influenced by outliers.

At 4 weeks and 12 weeks, change in the mean severity of moderate and severe hot flashes was –0.6 and –0.8 for 1,800-mg group vs. placebo. Change in frequency of these hot flashes was at the same statistical level at both time points for both dosing groups.

More than 60% of patients in both groups and more than 40% in the placebo group self-reported and were clinician reported as "very much improved" at 12 weeks. "This was a particularly high placebo response," said Dr. Utian.

Nonparametric analysis revealed a statistically significant change in median frequency of moderate to severe hot flashes at 4 weeks and 12 weeks in both active groups, compared with the placebo group.

Dizziness was the most commonly reported adverse event in both the 1,800-mg and 1,200-mg groups, whereas headache was most commonly reported in the placebo group. Somnolence was the second most common complaint in the active treatment groups. A total of 48 patients across both active treatment groups discontinued because of adverse events.

"Essentially, this long-release product was well tolerated, adverse events were mild, the difference was a slight difference in dizziness and somnolence during the titration, and [there was] no real difference in the adverse events" between the 1,800-mg and the 1,200-mg dosing regimens, said Dr. Utian. "The incidence of the adverse events declined markedly after 2-4 weeks of study therapy," he added.

Dr. Utian is a clinical consultant to Depomed Inc., the sponsor of the study. Some of the study investigators are Depomed employees.

CHICAGO – Almost 40% of women report sleep problems in midlife, and since hormone therapy benefits sleep, cessation of that therapy might have the opposite effect. A study of 1,704 women from the Group Health Research Institute of Seattle confirms that it does.

“Sleep problems were related to the suspension of hormone therapy for 1 or 2 months,” investigator Sarah E. Tom, Ph.D., formerly of the institute, said of the study’s findings. “Women who are discontinuing hormone therapy may benefit from alternative sleep management strategies immediately following discontinuation.” Dr. Tom presented her data at the annual meeting of the North American Menopause Society.

This was a secondary analysis of data from the READ study (Radiological Evaluation and Breast Density), a trial designed to test whether short-term suspension of hormone therapy resulted in better screening mammography performance. The trial recruited women aged 45-80 years from Group Health, a nonprofit health care system based in Washington state. The recruits were due for a screening mammography, and reported on use of hormone therapy for 2 years. They were randomized to continue hormone therapy or to suspend it for either 1 or 2 months prior to mammography.

The survey used a questionnaire that asked about the number of days subjects had various sleep complaints, including trouble falling asleep and waking while sleeping.

Various confounding variables, including alcohol consumption, body mass index, age, race, and ethnicity were considered, Dr. Tom said.

Of the 1,704 women, 1,405 had complete information on all variables. Of this group, 518 were randomized to continue hormone therapy, 452 to suspend therapy for 1 month, and 435 to suspend it for 2 months.

Demographic profiles were similar across all randomization groups. In the group continuing hormone therapy, for example, the median age was 58, more than 90% were white, and more than 50% used estrogen only. Sleep problems were comparable in the groups suspending therapy for 1 month or 2 months.

“For the group randomized to a 2-month suspension, they had an increase of about 0.7 days with trouble with their sleep, compared to women who were randomized to continue hormone therapy,” Dr. Tom said. Waking while sleeping was one of the most frequently reported problems, she said, and about 35% of women in the two sleep cessation groups reported using sleep aids in the previous week.

The study concluded that sleep problems were related to suspension of hormone therapy for 1 or 2 months. Dr. Tom said differences were modest but persistent across sleep items, and were similar for the 1- and 2-month suspension groups.

Dr. Tom disclosed no significant financial relationships. This study was sponsored by the Department of Defense, the National Institute on Aging, and the Group Health Research Institute.

CHICAGO – Almost 40% of women report sleep problems in midlife, and since hormone therapy benefits sleep, cessation of that therapy might have the opposite effect. A study of 1,704 women from the Group Health Research Institute of Seattle confirms that it does.

“Sleep problems were related to the suspension of hormone therapy for 1 or 2 months,” investigator Sarah E. Tom, Ph.D., formerly of the institute, said of the study’s findings. “Women who are discontinuing hormone therapy may benefit from alternative sleep management strategies immediately following discontinuation.” Dr. Tom presented her data at the annual meeting of the North American Menopause Society.

This was a secondary analysis of data from the READ study (Radiological Evaluation and Breast Density), a trial designed to test whether short-term suspension of hormone therapy resulted in better screening mammography performance. The trial recruited women aged 45-80 years from Group Health, a nonprofit health care system based in Washington state. The recruits were due for a screening mammography, and reported on use of hormone therapy for 2 years. They were randomized to continue hormone therapy or to suspend it for either 1 or 2 months prior to mammography.

The survey used a questionnaire that asked about the number of days subjects had various sleep complaints, including trouble falling asleep and waking while sleeping.

Various confounding variables, including alcohol consumption, body mass index, age, race, and ethnicity were considered, Dr. Tom said.

Of the 1,704 women, 1,405 had complete information on all variables. Of this group, 518 were randomized to continue hormone therapy, 452 to suspend therapy for 1 month, and 435 to suspend it for 2 months.

Demographic profiles were similar across all randomization groups. In the group continuing hormone therapy, for example, the median age was 58, more than 90% were white, and more than 50% used estrogen only. Sleep problems were comparable in the groups suspending therapy for 1 month or 2 months.

“For the group randomized to a 2-month suspension, they had an increase of about 0.7 days with trouble with their sleep, compared to women who were randomized to continue hormone therapy,” Dr. Tom said. Waking while sleeping was one of the most frequently reported problems, she said, and about 35% of women in the two sleep cessation groups reported using sleep aids in the previous week.

The study concluded that sleep problems were related to suspension of hormone therapy for 1 or 2 months. Dr. Tom said differences were modest but persistent across sleep items, and were similar for the 1- and 2-month suspension groups.

Dr. Tom disclosed no significant financial relationships. This study was sponsored by the Department of Defense, the National Institute on Aging, and the Group Health Research Institute.

CHICAGO – Almost 40% of women report sleep problems in midlife, and since hormone therapy benefits sleep, cessation of that therapy might have the opposite effect. A study of 1,704 women from the Group Health Research Institute of Seattle confirms that it does.

“Sleep problems were related to the suspension of hormone therapy for 1 or 2 months,” investigator Sarah E. Tom, Ph.D., formerly of the institute, said of the study’s findings. “Women who are discontinuing hormone therapy may benefit from alternative sleep management strategies immediately following discontinuation.” Dr. Tom presented her data at the annual meeting of the North American Menopause Society.

This was a secondary analysis of data from the READ study (Radiological Evaluation and Breast Density), a trial designed to test whether short-term suspension of hormone therapy resulted in better screening mammography performance. The trial recruited women aged 45-80 years from Group Health, a nonprofit health care system based in Washington state. The recruits were due for a screening mammography, and reported on use of hormone therapy for 2 years. They were randomized to continue hormone therapy or to suspend it for either 1 or 2 months prior to mammography.

The survey used a questionnaire that asked about the number of days subjects had various sleep complaints, including trouble falling asleep and waking while sleeping.

Various confounding variables, including alcohol consumption, body mass index, age, race, and ethnicity were considered, Dr. Tom said.

Of the 1,704 women, 1,405 had complete information on all variables. Of this group, 518 were randomized to continue hormone therapy, 452 to suspend therapy for 1 month, and 435 to suspend it for 2 months.

Demographic profiles were similar across all randomization groups. In the group continuing hormone therapy, for example, the median age was 58, more than 90% were white, and more than 50% used estrogen only. Sleep problems were comparable in the groups suspending therapy for 1 month or 2 months.

“For the group randomized to a 2-month suspension, they had an increase of about 0.7 days with trouble with their sleep, compared to women who were randomized to continue hormone therapy,” Dr. Tom said. Waking while sleeping was one of the most frequently reported problems, she said, and about 35% of women in the two sleep cessation groups reported using sleep aids in the previous week.

The study concluded that sleep problems were related to suspension of hormone therapy for 1 or 2 months. Dr. Tom said differences were modest but persistent across sleep items, and were similar for the 1- and 2-month suspension groups.

Dr. Tom disclosed no significant financial relationships. This study was sponsored by the Department of Defense, the National Institute on Aging, and the Group Health Research Institute.

CHICAGO — The patient on biologic therapy who must travel and requires immunization with a live attenuated virus or bacteria should be immunized before beginning biologic therapy, according to a case report presented to a symposium that was sponsored by the American College of Rheumatology.

“Think hard about the patient's life before you put them on biologic therapy, and immunize before you give the medications,” advised Dr. Clifton O. Bingham, who is director of the rheumatology clinics at Johns Hopkins University, Baltimore. However, he acknowledged that this would not always be possible.

The case was a 35-year-old woman with psoriatic arthritis whose work required her to travel to Burkina Faso, a small, landlocked country in West Africa, where yellow fever is endemic. The patient's skin and articular disease was well controlled with etanercept and methotrexate.

As a practical matter, Dr. Bingham said that the immunomodulators etanercept and methotrexate could be withheld for at least a period of 1 month, and then the patient could be administered yellow fever vaccine. He advised waiting 2-3 weeks before restarting the medication.

“The disease may flare during that period of time, so that's the risk you take,” he said.

If the patient was required to travel to the infected area with only 2 weeks' notice, Dr. Bingham advised providing a letter of medical contraindication to yellow fever vaccination.

“That should allow her to enter the country, but you tell her to be really careful.” When a patient is on biological therapy, he said it is important to understand which live vaccinations could potentially reactivate in the setting of immunosuppression.

Vaccines that contain live attenuated viruses or bacteria include varicella; intranasal influenza/H1N1; measles, mumps, and rubella; yellow fever; oral polio; oral typhoid; vaccinia (smallpox); BCG; and rotavirus.

Disseminated disease has been reported in immunocompromised patients who were immunized with live-virus vaccines. Live viral dissemination has occurred in patients during chemotherapy, and there have been cases of infection in patients receiving immunosuppression for organ transplantation. Live virus dissemination has also been reported in patients with HIV infection. (J. Infect. Dis. 2008;197 [Suppl 2]; Clin. Infect. Dis. 2009;49:1550-6; AIDS Rev. 2007;9:173-87). “So, the recommendation is, with people who are on biologics and people who are immunosuppressed, they should not receive these live vaccinations,” Dr. Bingham said.

Up-to-date vaccine information is available online from the Centers for Disease Control and Prevention (www.cdc.gov/vaccines/pubs/vis/default.htm

An audience member asked, “Do you think that in some cases it may be a better choice to subject somebody to the risk of an attenuated organism, as opposed to the risk of wild-type disease in an area where the disease may be highly endemic?”

Dr. Bingham said, “The risk of developing yellow fever is about 50 per 100,000 in western Africa, and about 10 per 100,000 in Central and South America. So it is a low risk.

“But if you delve a little deeper into that information, you find out that many of those patients die. It's potentially a fatal disease. So you do have to balance the risk.”

Disclosures: Dr. Bingham disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Centocor, Cypress Bioscience, Genentech, Merck, Novartis, Osiris Therapeutics, Procter & Gamble, Roche, Sonosite, Targeted Genetics, UCB, and Wyeth.

CHICAGO — The patient on biologic therapy who must travel and requires immunization with a live attenuated virus or bacteria should be immunized before beginning biologic therapy, according to a case report presented to a symposium that was sponsored by the American College of Rheumatology.

“Think hard about the patient's life before you put them on biologic therapy, and immunize before you give the medications,” advised Dr. Clifton O. Bingham, who is director of the rheumatology clinics at Johns Hopkins University, Baltimore. However, he acknowledged that this would not always be possible.

The case was a 35-year-old woman with psoriatic arthritis whose work required her to travel to Burkina Faso, a small, landlocked country in West Africa, where yellow fever is endemic. The patient's skin and articular disease was well controlled with etanercept and methotrexate.

As a practical matter, Dr. Bingham said that the immunomodulators etanercept and methotrexate could be withheld for at least a period of 1 month, and then the patient could be administered yellow fever vaccine. He advised waiting 2-3 weeks before restarting the medication.

“The disease may flare during that period of time, so that's the risk you take,” he said.

If the patient was required to travel to the infected area with only 2 weeks' notice, Dr. Bingham advised providing a letter of medical contraindication to yellow fever vaccination.

“That should allow her to enter the country, but you tell her to be really careful.” When a patient is on biological therapy, he said it is important to understand which live vaccinations could potentially reactivate in the setting of immunosuppression.

Vaccines that contain live attenuated viruses or bacteria include varicella; intranasal influenza/H1N1; measles, mumps, and rubella; yellow fever; oral polio; oral typhoid; vaccinia (smallpox); BCG; and rotavirus.

Disseminated disease has been reported in immunocompromised patients who were immunized with live-virus vaccines. Live viral dissemination has occurred in patients during chemotherapy, and there have been cases of infection in patients receiving immunosuppression for organ transplantation. Live virus dissemination has also been reported in patients with HIV infection. (J. Infect. Dis. 2008;197 [Suppl 2]; Clin. Infect. Dis. 2009;49:1550-6; AIDS Rev. 2007;9:173-87). “So, the recommendation is, with people who are on biologics and people who are immunosuppressed, they should not receive these live vaccinations,” Dr. Bingham said.

Up-to-date vaccine information is available online from the Centers for Disease Control and Prevention (www.cdc.gov/vaccines/pubs/vis/default.htm

An audience member asked, “Do you think that in some cases it may be a better choice to subject somebody to the risk of an attenuated organism, as opposed to the risk of wild-type disease in an area where the disease may be highly endemic?”

Dr. Bingham said, “The risk of developing yellow fever is about 50 per 100,000 in western Africa, and about 10 per 100,000 in Central and South America. So it is a low risk.

“But if you delve a little deeper into that information, you find out that many of those patients die. It's potentially a fatal disease. So you do have to balance the risk.”

Disclosures: Dr. Bingham disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Centocor, Cypress Bioscience, Genentech, Merck, Novartis, Osiris Therapeutics, Procter & Gamble, Roche, Sonosite, Targeted Genetics, UCB, and Wyeth.

CHICAGO — The patient on biologic therapy who must travel and requires immunization with a live attenuated virus or bacteria should be immunized before beginning biologic therapy, according to a case report presented to a symposium that was sponsored by the American College of Rheumatology.

“Think hard about the patient's life before you put them on biologic therapy, and immunize before you give the medications,” advised Dr. Clifton O. Bingham, who is director of the rheumatology clinics at Johns Hopkins University, Baltimore. However, he acknowledged that this would not always be possible.

The case was a 35-year-old woman with psoriatic arthritis whose work required her to travel to Burkina Faso, a small, landlocked country in West Africa, where yellow fever is endemic. The patient's skin and articular disease was well controlled with etanercept and methotrexate.

As a practical matter, Dr. Bingham said that the immunomodulators etanercept and methotrexate could be withheld for at least a period of 1 month, and then the patient could be administered yellow fever vaccine. He advised waiting 2-3 weeks before restarting the medication.

“The disease may flare during that period of time, so that's the risk you take,” he said.

If the patient was required to travel to the infected area with only 2 weeks' notice, Dr. Bingham advised providing a letter of medical contraindication to yellow fever vaccination.

“That should allow her to enter the country, but you tell her to be really careful.” When a patient is on biological therapy, he said it is important to understand which live vaccinations could potentially reactivate in the setting of immunosuppression.

Vaccines that contain live attenuated viruses or bacteria include varicella; intranasal influenza/H1N1; measles, mumps, and rubella; yellow fever; oral polio; oral typhoid; vaccinia (smallpox); BCG; and rotavirus.

Disseminated disease has been reported in immunocompromised patients who were immunized with live-virus vaccines. Live viral dissemination has occurred in patients during chemotherapy, and there have been cases of infection in patients receiving immunosuppression for organ transplantation. Live virus dissemination has also been reported in patients with HIV infection. (J. Infect. Dis. 2008;197 [Suppl 2]; Clin. Infect. Dis. 2009;49:1550-6; AIDS Rev. 2007;9:173-87). “So, the recommendation is, with people who are on biologics and people who are immunosuppressed, they should not receive these live vaccinations,” Dr. Bingham said.

Up-to-date vaccine information is available online from the Centers for Disease Control and Prevention (www.cdc.gov/vaccines/pubs/vis/default.htm

An audience member asked, “Do you think that in some cases it may be a better choice to subject somebody to the risk of an attenuated organism, as opposed to the risk of wild-type disease in an area where the disease may be highly endemic?”

Dr. Bingham said, “The risk of developing yellow fever is about 50 per 100,000 in western Africa, and about 10 per 100,000 in Central and South America. So it is a low risk.

“But if you delve a little deeper into that information, you find out that many of those patients die. It's potentially a fatal disease. So you do have to balance the risk.”

Disclosures: Dr. Bingham disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Centocor, Cypress Bioscience, Genentech, Merck, Novartis, Osiris Therapeutics, Procter & Gamble, Roche, Sonosite, Targeted Genetics, UCB, and Wyeth.