Michele G. Sullivan

ROME – Ultrasound identification of subclinical synovitis allowed clinicians to get the upper hand on early joint damage in rheumatoid arthritis patients who were in remission.

When these patients increased their methotrexate for 52 weeks, follow-up imaging showed that burgeoning joint damage had arrested, Dr. Tadashi Okano said at the annual meeting of the European League Against Rheumatism. The findings suggest that even patients in clinical remission can have subclinically active disease, which can be identified and effectively managed.

“Although the latest recommendations for the treatment of rheumatoid arthritis focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis...should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom free,” said Dr. Okano of the Osaka City University Graduate School of Medicine, Japan.

Dr. Okano investigated the potential benefit of intensifying treatment for patients who, although in remission, had ultrasound-diagnosed synovitis. The study comprised 134 patients; most (101) had subclinical synovitis as graded by the power Doppler ultrasound score (PDUS). They were randomized to either maintain their methotrexate dosage or to an increased dosage, for 52 weeks. The 33 patients without synovitis served as a control group. Standard radiographs of hands and feet were obtained at baseline, and weeks 24 and 52. Radiological joint damage was assessed according to the modified total Sharp score (mTSS).

By 52 weeks, the total PDUS had decreased significantly more in the intensified methotrexate group than in the stable methotrexate group (–3.9 vs. –2.0 points). Synovitis progression as graded by the mTSS was significantly suppressed in the intensified treatment group as well, both at week 24 (0.27 vs. 1.02) and week 52 (1.03 vs. 2.02).

The improvement was even more pronounced in the subset of 16 patients who were also taking biologics, Dr. Okano said. Joint damage in these patients was suppressed to the point where they resembled patients free of synovitis, with mTSS scores of 0.75 and 0.80, respectively.

“Subclinical active synovitis should be controlled by additional treatment, as this results in the prevention of the joint damage progression, Dr. Okano noted. High-resolution ultrasound offers the chance to identify these patients for early, aggressive management.

Dr. Okano had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

ROME – Ultrasound identification of subclinical synovitis allowed clinicians to get the upper hand on early joint damage in rheumatoid arthritis patients who were in remission.

When these patients increased their methotrexate for 52 weeks, follow-up imaging showed that burgeoning joint damage had arrested, Dr. Tadashi Okano said at the annual meeting of the European League Against Rheumatism. The findings suggest that even patients in clinical remission can have subclinically active disease, which can be identified and effectively managed.

“Although the latest recommendations for the treatment of rheumatoid arthritis focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis...should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom free,” said Dr. Okano of the Osaka City University Graduate School of Medicine, Japan.

Dr. Okano investigated the potential benefit of intensifying treatment for patients who, although in remission, had ultrasound-diagnosed synovitis. The study comprised 134 patients; most (101) had subclinical synovitis as graded by the power Doppler ultrasound score (PDUS). They were randomized to either maintain their methotrexate dosage or to an increased dosage, for 52 weeks. The 33 patients without synovitis served as a control group. Standard radiographs of hands and feet were obtained at baseline, and weeks 24 and 52. Radiological joint damage was assessed according to the modified total Sharp score (mTSS).

By 52 weeks, the total PDUS had decreased significantly more in the intensified methotrexate group than in the stable methotrexate group (–3.9 vs. –2.0 points). Synovitis progression as graded by the mTSS was significantly suppressed in the intensified treatment group as well, both at week 24 (0.27 vs. 1.02) and week 52 (1.03 vs. 2.02).

The improvement was even more pronounced in the subset of 16 patients who were also taking biologics, Dr. Okano said. Joint damage in these patients was suppressed to the point where they resembled patients free of synovitis, with mTSS scores of 0.75 and 0.80, respectively.

“Subclinical active synovitis should be controlled by additional treatment, as this results in the prevention of the joint damage progression, Dr. Okano noted. High-resolution ultrasound offers the chance to identify these patients for early, aggressive management.

Dr. Okano had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

ROME – Ultrasound identification of subclinical synovitis allowed clinicians to get the upper hand on early joint damage in rheumatoid arthritis patients who were in remission.

When these patients increased their methotrexate for 52 weeks, follow-up imaging showed that burgeoning joint damage had arrested, Dr. Tadashi Okano said at the annual meeting of the European League Against Rheumatism. The findings suggest that even patients in clinical remission can have subclinically active disease, which can be identified and effectively managed.

“Although the latest recommendations for the treatment of rheumatoid arthritis focus on the achievement of clinical remission, we have demonstrated that patients with subclinical synovitis...should be treated more intensively to reduce the risk of further joint destruction, even when the patient is currently symptom free,” said Dr. Okano of the Osaka City University Graduate School of Medicine, Japan.

Dr. Okano investigated the potential benefit of intensifying treatment for patients who, although in remission, had ultrasound-diagnosed synovitis. The study comprised 134 patients; most (101) had subclinical synovitis as graded by the power Doppler ultrasound score (PDUS). They were randomized to either maintain their methotrexate dosage or to an increased dosage, for 52 weeks. The 33 patients without synovitis served as a control group. Standard radiographs of hands and feet were obtained at baseline, and weeks 24 and 52. Radiological joint damage was assessed according to the modified total Sharp score (mTSS).

By 52 weeks, the total PDUS had decreased significantly more in the intensified methotrexate group than in the stable methotrexate group (–3.9 vs. –2.0 points). Synovitis progression as graded by the mTSS was significantly suppressed in the intensified treatment group as well, both at week 24 (0.27 vs. 1.02) and week 52 (1.03 vs. 2.02).

The improvement was even more pronounced in the subset of 16 patients who were also taking biologics, Dr. Okano said. Joint damage in these patients was suppressed to the point where they resembled patients free of synovitis, with mTSS scores of 0.75 and 0.80, respectively.

“Subclinical active synovitis should be controlled by additional treatment, as this results in the prevention of the joint damage progression, Dr. Okano noted. High-resolution ultrasound offers the chance to identify these patients for early, aggressive management.

Dr. Okano had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Patients with newly diagnosed rheumatoid arthritis already show increased aortic stiffness as well as lower left and right ventricular, end-systolic, and end-diastolic volumes, Dr. Maya Buch reported at the European Congress of Rheumatology.

The imaging findings lend support to a growing view that inflammation may underlie cardiovascular as well as rheumatic disease, Dr. Buch said in an interview.

“Rheumatoid arthritis is associated with increased cardiovascular disease and death. This is thought to be due to the inflammatory drive as well as traditional risk factors,” said Dr. Buch of the University of Leeds (England). “There is also a significant literature base suggesting atherosclerosis is inflammation driven, thus, shared mechanisms are likely.”

Dr. Buch and her colleagues conducted cardiac magnetic resonance imaging studies on 66 patients with early rheumatoid arthritis; all were treatment naive and had symptoms of less than 1 year in duration. They were matched for age, gender, and blood pressure with 30 healthy controls.

Patients had a mean age of about 48 years; mean systolic blood pressures were similar – 122 mm Hg for patients and 126 mm Hg for controls.

In the patients, the median erythrocyte sedimentation rate was 39.5 mm/hr; C-reactive protein was 18.9 mg/L. The mean Disease Activity Score 28 was 5.65. Most (82%) were positive for anticitrullinated protein antibodies; 73% were positive for rheumatoid factors.

Patients showed significantly reduced aortic distensibility, compared with controls. Aortic compliance and aortic strain were also significantly lower in patients, while aortic stiffness was significantly higher.

Evidence of early cardiac remodeling was present. Left ventricular and right ventricular end-systolic and end-diastolic volumes were all lower in the patients. A trend for lower left ventricular mass index seemed to be associated with seropositivity, Dr. Buch noted. Four patients showed evidence of overt inflammation or fibrosis with focal nonischemic patterns of late gadolinium enhancement.

These changes suggest an early cardiomyopathy, Dr. Buch said, and could imply a higher risk for cardiovascular morbidity and mortality at time of diagnosis. She added that the next steps in learning about this association will be to clarify its natural history, clinical implications, and the potential to modify outcomes with effective therapy. Although these new data are striking, they aren’t enough to recommend that newly diagnosed patients get routine cardiac imaging, Dr. Buch said.

“The study clearly implies that subclinical cardiovascular pathology exists at the early stage. Screening wouldn’t be appropriate at this stage – the clinical outcome and relevance of subclinical disease is not yet clear. However further evaluation will clarify whether additional benefits of RA disease control – for example, improving the cardiovascular risk and abnormalities seen here – are possible. This could influence future management approach.”

[email protected]

Patients with newly diagnosed rheumatoid arthritis already show increased aortic stiffness as well as lower left and right ventricular, end-systolic, and end-diastolic volumes, Dr. Maya Buch reported at the European Congress of Rheumatology.

The imaging findings lend support to a growing view that inflammation may underlie cardiovascular as well as rheumatic disease, Dr. Buch said in an interview.

“Rheumatoid arthritis is associated with increased cardiovascular disease and death. This is thought to be due to the inflammatory drive as well as traditional risk factors,” said Dr. Buch of the University of Leeds (England). “There is also a significant literature base suggesting atherosclerosis is inflammation driven, thus, shared mechanisms are likely.”

Dr. Buch and her colleagues conducted cardiac magnetic resonance imaging studies on 66 patients with early rheumatoid arthritis; all were treatment naive and had symptoms of less than 1 year in duration. They were matched for age, gender, and blood pressure with 30 healthy controls.

Patients had a mean age of about 48 years; mean systolic blood pressures were similar – 122 mm Hg for patients and 126 mm Hg for controls.

In the patients, the median erythrocyte sedimentation rate was 39.5 mm/hr; C-reactive protein was 18.9 mg/L. The mean Disease Activity Score 28 was 5.65. Most (82%) were positive for anticitrullinated protein antibodies; 73% were positive for rheumatoid factors.

Patients showed significantly reduced aortic distensibility, compared with controls. Aortic compliance and aortic strain were also significantly lower in patients, while aortic stiffness was significantly higher.

Evidence of early cardiac remodeling was present. Left ventricular and right ventricular end-systolic and end-diastolic volumes were all lower in the patients. A trend for lower left ventricular mass index seemed to be associated with seropositivity, Dr. Buch noted. Four patients showed evidence of overt inflammation or fibrosis with focal nonischemic patterns of late gadolinium enhancement.

These changes suggest an early cardiomyopathy, Dr. Buch said, and could imply a higher risk for cardiovascular morbidity and mortality at time of diagnosis. She added that the next steps in learning about this association will be to clarify its natural history, clinical implications, and the potential to modify outcomes with effective therapy. Although these new data are striking, they aren’t enough to recommend that newly diagnosed patients get routine cardiac imaging, Dr. Buch said.

“The study clearly implies that subclinical cardiovascular pathology exists at the early stage. Screening wouldn’t be appropriate at this stage – the clinical outcome and relevance of subclinical disease is not yet clear. However further evaluation will clarify whether additional benefits of RA disease control – for example, improving the cardiovascular risk and abnormalities seen here – are possible. This could influence future management approach.”

[email protected]

Patients with newly diagnosed rheumatoid arthritis already show increased aortic stiffness as well as lower left and right ventricular, end-systolic, and end-diastolic volumes, Dr. Maya Buch reported at the European Congress of Rheumatology.

The imaging findings lend support to a growing view that inflammation may underlie cardiovascular as well as rheumatic disease, Dr. Buch said in an interview.

“Rheumatoid arthritis is associated with increased cardiovascular disease and death. This is thought to be due to the inflammatory drive as well as traditional risk factors,” said Dr. Buch of the University of Leeds (England). “There is also a significant literature base suggesting atherosclerosis is inflammation driven, thus, shared mechanisms are likely.”

Dr. Buch and her colleagues conducted cardiac magnetic resonance imaging studies on 66 patients with early rheumatoid arthritis; all were treatment naive and had symptoms of less than 1 year in duration. They were matched for age, gender, and blood pressure with 30 healthy controls.

Patients had a mean age of about 48 years; mean systolic blood pressures were similar – 122 mm Hg for patients and 126 mm Hg for controls.

In the patients, the median erythrocyte sedimentation rate was 39.5 mm/hr; C-reactive protein was 18.9 mg/L. The mean Disease Activity Score 28 was 5.65. Most (82%) were positive for anticitrullinated protein antibodies; 73% were positive for rheumatoid factors.

Patients showed significantly reduced aortic distensibility, compared with controls. Aortic compliance and aortic strain were also significantly lower in patients, while aortic stiffness was significantly higher.

Evidence of early cardiac remodeling was present. Left ventricular and right ventricular end-systolic and end-diastolic volumes were all lower in the patients. A trend for lower left ventricular mass index seemed to be associated with seropositivity, Dr. Buch noted. Four patients showed evidence of overt inflammation or fibrosis with focal nonischemic patterns of late gadolinium enhancement.

These changes suggest an early cardiomyopathy, Dr. Buch said, and could imply a higher risk for cardiovascular morbidity and mortality at time of diagnosis. She added that the next steps in learning about this association will be to clarify its natural history, clinical implications, and the potential to modify outcomes with effective therapy. Although these new data are striking, they aren’t enough to recommend that newly diagnosed patients get routine cardiac imaging, Dr. Buch said.

“The study clearly implies that subclinical cardiovascular pathology exists at the early stage. Screening wouldn’t be appropriate at this stage – the clinical outcome and relevance of subclinical disease is not yet clear. However further evaluation will clarify whether additional benefits of RA disease control – for example, improving the cardiovascular risk and abnormalities seen here – are possible. This could influence future management approach.”

[email protected]

Pregnancy may not increase the risk of a cardiovascular event (CVE) in women with systemic lupus erythematosus as much as disease-related morbidities, according to findings from a large, retrospective study presented at the European Congress of Rheumatology.

In fact, uncomplicated pregnancy may be a positive marker for later cardiovascular health in lupus patients, Dr. May Ching Soh reported at the meeting.

“Physicians and patients may derive some reassurance that perhaps a pregnancy uncomplicated by maternal-placental pathology may be associated with lower risk for future cardiovascular events,” Dr. Soh said in an interview. “However, we cannot at this time recommend relaxing on our laurels and not screening and actively managing cardiovascular risk factors in all patients with systemic lupus erythematosus.”

Dr. Soh, an obstetrician in the Women’s Centre at Oxford Radcliffe Hospital, part of the Oxford (England) University Hospitals NHS Trust, extracted data from linked Swedish population registries on systemic lupus erythematosus (SLE) patients’ parity status, the occurrence of features of maternal-placental syndrome (MPS, defined as hypertensive disorders of pregnancy, small-for-gestational-age, stillbirth, and placental abruption), SLE-related morbidities (in-patient admissions, renal disease, malignancies, and infections), and CVE outcomes (coronary artery disease, stroke, peripheral vascular disease, and death from these causes).

The final cohort comprised 3,232 women with SLE who had been born in 1951-1971. A total of 72% had children.

The mean age at follow-up was 49 years. Nulliparous women had more SLE-related morbidities, more cardiovascular risk factors, and more cardiovascular events than did parous women.

CVEs were most common among those women who had never given birth (3.4 per 1,000 person-years), followed by women with pregnancies complicated by MPS (2.8 per 1,000 person-years). Compared with women who had an uncomplicated pregnancy, the risk of a CVE was doubled in the nulliparous group (hazard ratio, 2.2) and close to double in the MPS-pregnancy group (HR, 1.8).

The time to first CVE also was significantly delayed in women who had uncomplicated pregnancies. By age 30, almost none had occurred in these women, but 5% of those with MPS-complicated pregnancies and 10% of the nulliparous women had experienced an event by that age. The separation continued as women aged. By age 40, an event had occurred in about 4% of the MPS-free women, 8% of the MPS group, and 10% of the nulliparous group. The rates at age 45 were 5%, 8%, and 15%, respectively.

“Our nonparous cohort did develop cardiovascular events earlier, but the MPS cohort also had accelerated development compared to the women who had uncomplicated pregnancies,” Dr. Soh said. “In fact, an adverse pregnancy outcome should serve as a red flag for physicians to start screening early for cardiovascular disease and actively managing risk factors.”

She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Pregnancy may not increase the risk of a cardiovascular event (CVE) in women with systemic lupus erythematosus as much as disease-related morbidities, according to findings from a large, retrospective study presented at the European Congress of Rheumatology.

In fact, uncomplicated pregnancy may be a positive marker for later cardiovascular health in lupus patients, Dr. May Ching Soh reported at the meeting.

“Physicians and patients may derive some reassurance that perhaps a pregnancy uncomplicated by maternal-placental pathology may be associated with lower risk for future cardiovascular events,” Dr. Soh said in an interview. “However, we cannot at this time recommend relaxing on our laurels and not screening and actively managing cardiovascular risk factors in all patients with systemic lupus erythematosus.”

Dr. Soh, an obstetrician in the Women’s Centre at Oxford Radcliffe Hospital, part of the Oxford (England) University Hospitals NHS Trust, extracted data from linked Swedish population registries on systemic lupus erythematosus (SLE) patients’ parity status, the occurrence of features of maternal-placental syndrome (MPS, defined as hypertensive disorders of pregnancy, small-for-gestational-age, stillbirth, and placental abruption), SLE-related morbidities (in-patient admissions, renal disease, malignancies, and infections), and CVE outcomes (coronary artery disease, stroke, peripheral vascular disease, and death from these causes).

The final cohort comprised 3,232 women with SLE who had been born in 1951-1971. A total of 72% had children.

The mean age at follow-up was 49 years. Nulliparous women had more SLE-related morbidities, more cardiovascular risk factors, and more cardiovascular events than did parous women.

CVEs were most common among those women who had never given birth (3.4 per 1,000 person-years), followed by women with pregnancies complicated by MPS (2.8 per 1,000 person-years). Compared with women who had an uncomplicated pregnancy, the risk of a CVE was doubled in the nulliparous group (hazard ratio, 2.2) and close to double in the MPS-pregnancy group (HR, 1.8).

The time to first CVE also was significantly delayed in women who had uncomplicated pregnancies. By age 30, almost none had occurred in these women, but 5% of those with MPS-complicated pregnancies and 10% of the nulliparous women had experienced an event by that age. The separation continued as women aged. By age 40, an event had occurred in about 4% of the MPS-free women, 8% of the MPS group, and 10% of the nulliparous group. The rates at age 45 were 5%, 8%, and 15%, respectively.

“Our nonparous cohort did develop cardiovascular events earlier, but the MPS cohort also had accelerated development compared to the women who had uncomplicated pregnancies,” Dr. Soh said. “In fact, an adverse pregnancy outcome should serve as a red flag for physicians to start screening early for cardiovascular disease and actively managing risk factors.”

She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Pregnancy may not increase the risk of a cardiovascular event (CVE) in women with systemic lupus erythematosus as much as disease-related morbidities, according to findings from a large, retrospective study presented at the European Congress of Rheumatology.

In fact, uncomplicated pregnancy may be a positive marker for later cardiovascular health in lupus patients, Dr. May Ching Soh reported at the meeting.

“Physicians and patients may derive some reassurance that perhaps a pregnancy uncomplicated by maternal-placental pathology may be associated with lower risk for future cardiovascular events,” Dr. Soh said in an interview. “However, we cannot at this time recommend relaxing on our laurels and not screening and actively managing cardiovascular risk factors in all patients with systemic lupus erythematosus.”

Dr. Soh, an obstetrician in the Women’s Centre at Oxford Radcliffe Hospital, part of the Oxford (England) University Hospitals NHS Trust, extracted data from linked Swedish population registries on systemic lupus erythematosus (SLE) patients’ parity status, the occurrence of features of maternal-placental syndrome (MPS, defined as hypertensive disorders of pregnancy, small-for-gestational-age, stillbirth, and placental abruption), SLE-related morbidities (in-patient admissions, renal disease, malignancies, and infections), and CVE outcomes (coronary artery disease, stroke, peripheral vascular disease, and death from these causes).

The final cohort comprised 3,232 women with SLE who had been born in 1951-1971. A total of 72% had children.

The mean age at follow-up was 49 years. Nulliparous women had more SLE-related morbidities, more cardiovascular risk factors, and more cardiovascular events than did parous women.

CVEs were most common among those women who had never given birth (3.4 per 1,000 person-years), followed by women with pregnancies complicated by MPS (2.8 per 1,000 person-years). Compared with women who had an uncomplicated pregnancy, the risk of a CVE was doubled in the nulliparous group (hazard ratio, 2.2) and close to double in the MPS-pregnancy group (HR, 1.8).

The time to first CVE also was significantly delayed in women who had uncomplicated pregnancies. By age 30, almost none had occurred in these women, but 5% of those with MPS-complicated pregnancies and 10% of the nulliparous women had experienced an event by that age. The separation continued as women aged. By age 40, an event had occurred in about 4% of the MPS-free women, 8% of the MPS group, and 10% of the nulliparous group. The rates at age 45 were 5%, 8%, and 15%, respectively.

“Our nonparous cohort did develop cardiovascular events earlier, but the MPS cohort also had accelerated development compared to the women who had uncomplicated pregnancies,” Dr. Soh said. “In fact, an adverse pregnancy outcome should serve as a red flag for physicians to start screening early for cardiovascular disease and actively managing risk factors.”

She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

NEW ORLEANS – Men with cardiac problems appear to have a high rate of symptomatic hypogonadism, according to a study conducted in one of the nation’s largest cardiology practices.

Low testosterone was seven times more prevalent among those patients than among the general population, Dr. Tobias Köhler said at the annual meeting of the American Urological Association.

Erectile dysfunction – untreated in most cases – along with benign prostatic hypertrophy and lower urinary tract symptoms were highly prevalent among these patients. These findings raise an important question for cardiologists, said Dr. Köhler, who is chief of the division of male infertility at the Southern Illinois University’s Fertility and IVF Center in Carbondale.

“Does this mean we should be screening cardiac patients for hypogonadism and these other issues? The results of this study suggest that we should. We have an opportunity to intervene early here.”

Dr. Köhler conducted the CUPID (Cardio-Urologic Pathology/Prevalence Interplay Determination) study in a large group cardiology practice and assessed symptomatic hypogonadism and urologic symptoms in patients who presented to the cardiology service. He queried patients using the international index of erectile function questionnaire (IIEF), the international prostate symptom score, and the ADAM low testosterone survey. He also obtained measures of cholesterol, total testosterone, free testosterone, and the testosterone/estradiol ratio. Men were considered biochemically hypogonadal if the total testosterone was below 300 ng/dL; the calculated free testosterone was below 6.5 ng/dL; and the ratio was below 10.

He enrolled 200 patents, mean age 67 years. The mean body mass index was 32 kg/m^2. Mean total testosterone was 310 ng/mL, but the range was wide (32 ng/dL to 1,156 ng/dL). Sex hormone binding globulin averaged 42 nmol/mL and calculated free testosterone was 5.4 mg/dL.

More than half of the men were below the lowest reference range in total testosterone (54%), calculated free testosterone (79%), and free testosterone (70%).

About 72% of these men also had symptoms of low testosterone. “This is a sevenfold increase in symptomatic hypogonadism over the general population,” Dr. Köhler said.

Many men had erectile dysfunction, a finding that increased with age. By standards of the National Health and Nutrition Examination Score, 15% of those aged 40-59 years had ED – a significantly increased risk ratio of 3.2 compared to the general population. For older men the rate was still higher, although not significantly so.

“The vast majority of these men were untreated medically,” and had never tried any other form of intervention, Dr. Köhler said. “This is clearly an undertreated population. It represents a big treatment gap and a window of opportunity to treat ED in young men with heart disease.”

With regard to lower urinary tract symptom scores, Dr. Köhler found that low testosterone was primarily associated with storage symptoms. About 25% of those with low testosterone levels had symptoms of frequency and urgency compared with 15% of those with normal levels of testosterone. It was also associated with incomplete voiding.

“A 4-point worsening in storage symptoms was associated with a decrease in calculated free testosterone of 0.88 ng/dL,” he said. Age and body mass index were also significantly associated with low testosterone.

However, erectile dysfunction was not significantly related to low testosterone levels. The only independent predictors for ED were age and the patient’s total number of medications. Similarly, there was no significant relationship between low levels and ejaculatory function; this was predicted only by the IIEF score, coronary artery bypass grafting, and antidepressants.

Dr. Köhler’s work has inspired the cardiology practice to participate in a number of changes. “They have amended their review of symptoms to include questions about erectile dysfunction, and we are now also participating in the ZEN trial – the first-in-man study of pudendal artery stents for ED. It looks like we can cure ED with these – in the right patients.”

He also has continued CUPID as a prospective cohort study that will follow the group. “Some of these men will elect testosterone replacement and some will not. This gives us a great opportunity to assess cardiac outcomes and interventions – I’m especially interested in the role of exercise.”

Dr. Köhler had no financial disclosures.

[email protected]

NEW ORLEANS – Men with cardiac problems appear to have a high rate of symptomatic hypogonadism, according to a study conducted in one of the nation’s largest cardiology practices.

Low testosterone was seven times more prevalent among those patients than among the general population, Dr. Tobias Köhler said at the annual meeting of the American Urological Association.

Erectile dysfunction – untreated in most cases – along with benign prostatic hypertrophy and lower urinary tract symptoms were highly prevalent among these patients. These findings raise an important question for cardiologists, said Dr. Köhler, who is chief of the division of male infertility at the Southern Illinois University’s Fertility and IVF Center in Carbondale.

“Does this mean we should be screening cardiac patients for hypogonadism and these other issues? The results of this study suggest that we should. We have an opportunity to intervene early here.”

Dr. Köhler conducted the CUPID (Cardio-Urologic Pathology/Prevalence Interplay Determination) study in a large group cardiology practice and assessed symptomatic hypogonadism and urologic symptoms in patients who presented to the cardiology service. He queried patients using the international index of erectile function questionnaire (IIEF), the international prostate symptom score, and the ADAM low testosterone survey. He also obtained measures of cholesterol, total testosterone, free testosterone, and the testosterone/estradiol ratio. Men were considered biochemically hypogonadal if the total testosterone was below 300 ng/dL; the calculated free testosterone was below 6.5 ng/dL; and the ratio was below 10.

He enrolled 200 patents, mean age 67 years. The mean body mass index was 32 kg/m^2. Mean total testosterone was 310 ng/mL, but the range was wide (32 ng/dL to 1,156 ng/dL). Sex hormone binding globulin averaged 42 nmol/mL and calculated free testosterone was 5.4 mg/dL.

More than half of the men were below the lowest reference range in total testosterone (54%), calculated free testosterone (79%), and free testosterone (70%).

About 72% of these men also had symptoms of low testosterone. “This is a sevenfold increase in symptomatic hypogonadism over the general population,” Dr. Köhler said.

Many men had erectile dysfunction, a finding that increased with age. By standards of the National Health and Nutrition Examination Score, 15% of those aged 40-59 years had ED – a significantly increased risk ratio of 3.2 compared to the general population. For older men the rate was still higher, although not significantly so.

“The vast majority of these men were untreated medically,” and had never tried any other form of intervention, Dr. Köhler said. “This is clearly an undertreated population. It represents a big treatment gap and a window of opportunity to treat ED in young men with heart disease.”

With regard to lower urinary tract symptom scores, Dr. Köhler found that low testosterone was primarily associated with storage symptoms. About 25% of those with low testosterone levels had symptoms of frequency and urgency compared with 15% of those with normal levels of testosterone. It was also associated with incomplete voiding.

“A 4-point worsening in storage symptoms was associated with a decrease in calculated free testosterone of 0.88 ng/dL,” he said. Age and body mass index were also significantly associated with low testosterone.

However, erectile dysfunction was not significantly related to low testosterone levels. The only independent predictors for ED were age and the patient’s total number of medications. Similarly, there was no significant relationship between low levels and ejaculatory function; this was predicted only by the IIEF score, coronary artery bypass grafting, and antidepressants.

Dr. Köhler’s work has inspired the cardiology practice to participate in a number of changes. “They have amended their review of symptoms to include questions about erectile dysfunction, and we are now also participating in the ZEN trial – the first-in-man study of pudendal artery stents for ED. It looks like we can cure ED with these – in the right patients.”

He also has continued CUPID as a prospective cohort study that will follow the group. “Some of these men will elect testosterone replacement and some will not. This gives us a great opportunity to assess cardiac outcomes and interventions – I’m especially interested in the role of exercise.”

Dr. Köhler had no financial disclosures.

[email protected]

NEW ORLEANS – Men with cardiac problems appear to have a high rate of symptomatic hypogonadism, according to a study conducted in one of the nation’s largest cardiology practices.

Low testosterone was seven times more prevalent among those patients than among the general population, Dr. Tobias Köhler said at the annual meeting of the American Urological Association.

Erectile dysfunction – untreated in most cases – along with benign prostatic hypertrophy and lower urinary tract symptoms were highly prevalent among these patients. These findings raise an important question for cardiologists, said Dr. Köhler, who is chief of the division of male infertility at the Southern Illinois University’s Fertility and IVF Center in Carbondale.

“Does this mean we should be screening cardiac patients for hypogonadism and these other issues? The results of this study suggest that we should. We have an opportunity to intervene early here.”

Dr. Köhler conducted the CUPID (Cardio-Urologic Pathology/Prevalence Interplay Determination) study in a large group cardiology practice and assessed symptomatic hypogonadism and urologic symptoms in patients who presented to the cardiology service. He queried patients using the international index of erectile function questionnaire (IIEF), the international prostate symptom score, and the ADAM low testosterone survey. He also obtained measures of cholesterol, total testosterone, free testosterone, and the testosterone/estradiol ratio. Men were considered biochemically hypogonadal if the total testosterone was below 300 ng/dL; the calculated free testosterone was below 6.5 ng/dL; and the ratio was below 10.

He enrolled 200 patents, mean age 67 years. The mean body mass index was 32 kg/m^2. Mean total testosterone was 310 ng/mL, but the range was wide (32 ng/dL to 1,156 ng/dL). Sex hormone binding globulin averaged 42 nmol/mL and calculated free testosterone was 5.4 mg/dL.

More than half of the men were below the lowest reference range in total testosterone (54%), calculated free testosterone (79%), and free testosterone (70%).

About 72% of these men also had symptoms of low testosterone. “This is a sevenfold increase in symptomatic hypogonadism over the general population,” Dr. Köhler said.

Many men had erectile dysfunction, a finding that increased with age. By standards of the National Health and Nutrition Examination Score, 15% of those aged 40-59 years had ED – a significantly increased risk ratio of 3.2 compared to the general population. For older men the rate was still higher, although not significantly so.

“The vast majority of these men were untreated medically,” and had never tried any other form of intervention, Dr. Köhler said. “This is clearly an undertreated population. It represents a big treatment gap and a window of opportunity to treat ED in young men with heart disease.”

With regard to lower urinary tract symptom scores, Dr. Köhler found that low testosterone was primarily associated with storage symptoms. About 25% of those with low testosterone levels had symptoms of frequency and urgency compared with 15% of those with normal levels of testosterone. It was also associated with incomplete voiding.

“A 4-point worsening in storage symptoms was associated with a decrease in calculated free testosterone of 0.88 ng/dL,” he said. Age and body mass index were also significantly associated with low testosterone.

However, erectile dysfunction was not significantly related to low testosterone levels. The only independent predictors for ED were age and the patient’s total number of medications. Similarly, there was no significant relationship between low levels and ejaculatory function; this was predicted only by the IIEF score, coronary artery bypass grafting, and antidepressants.

Dr. Köhler’s work has inspired the cardiology practice to participate in a number of changes. “They have amended their review of symptoms to include questions about erectile dysfunction, and we are now also participating in the ZEN trial – the first-in-man study of pudendal artery stents for ED. It looks like we can cure ED with these – in the right patients.”

He also has continued CUPID as a prospective cohort study that will follow the group. “Some of these men will elect testosterone replacement and some will not. This gives us a great opportunity to assess cardiac outcomes and interventions – I’m especially interested in the role of exercise.”

Dr. Köhler had no financial disclosures.

[email protected]

NEW ORLEANS – Long-term active surveillance seems to be a safe and effective way to avoid overtreatment in men with low- and very low-risk prostate cancer, while still offering a very good chance of catching progressive disease.

According to new data presented at the annual meeting of the American Urological Association, less than 3% of men developed metastatic disease or died from prostate cancer over 15 years of follow-up. The men’s risk of progression dramatically declined over time, decreasing by 30% after each annual, unchanged biopsy.

The findings should reassure both physicians and patients, all of whom want to balance the potential side effects of prostate cancer treatment with the risk of progressive disease, said Dr. Stacy Loeb of New York University, New York.

“Physicians in the U.S. have been slow to adopt the practice of active surveillance, which is much more common in other parts of the world,” said Dr. Loeb, who moderated the press briefing where the data were unveiled. She has worked with Swedish researchers, who determined that 84% of men with very low-risk cancers and 66% of those with low-risk cancers are being managed this way. “The question we have to ask is why we have been so slow to adopt this. Hopefully, studies like these, showing so many men free of disease even at 15 years, will encourage greater acceptance in this country.”

The briefing highlighted several studies on active surveillance; two of these were performed on the Johns Hopkins Active Surveillance Program cohort, which has enrolled about 1,300 men since 1995. Most (71%) have very low-risk cancer; the remainder have low-risk cancer.

The Hopkins protocol calls for a clinical exam and prostate specific antigen (PSA) test twice a year, annual prostate biopsy, and imaging every either year, said Dr. Jeffrey Tosoian, a urology resident at the university.

Triggers for treatment include a change in biopsy or patient decision. Changes in PSA and clinical exam alone don’t trigger treatment, but may prompt a stepped-up monitoring schedule or additional diagnostic studies.

The Hopkins cohort is a fairly typical prostate cancer group. The patients’ mean age at diagnosis is about 66 years, and their mean PSA level is 5.2 ng/mL. Mean follow-up time is now 5 years, but Dr. Tosoian also presented 10- and 15-year data.

At 5 years, 36% of the group had converted to some form of treatment. By 10 and 15 years, conversion had occurred in 50% and 56%, respectively. Not surprisingly, the rate of death from any cause increased as patients aged, from 4% by year 5, to 7% and 31% by years 10 and 15.

But the rate of prostate cancer-specific death was very low throughout the study period: 0.15% at year 5 and 1% at years 10 and 15. Over the entire 15 years, less than 1% of the men died from prostate cancer or developed metastatic disease.

These findings were somewhat more positive than those recently reported by a team at Sunnybrook University, Toronto (J. Clin. Oncol. 2015;33:272-7). That surveillance protocol is less stringent than the one at Hopkins, Dr. Tosoian said, with biopsies every 3-5 years, based on clinical findings and PSA levels.

In that cohort of 819 patients with a median follow-up of 6 years, 3% developed metastatic disease by 15 years and 1.5% died from it, but the men were nine times more likely to die from some other cause than their cancer.

“Certainly, our more intensive monitoring at Hopkins was associated with more treatment, but also with lower death and metastatic rates,” Dr. Tosoian said. “So there are still trade-offs in balancing overtreatment, but the real risk of cancer mortality is quite small.”

However, the question of how long must watchful waiting continue remains. Understandably, most men don’t want to commit to years and years of annual prostate biopsies, said Dr. Ridwan Alam, also of Johns Hopkins.

Dr. Alam presented 15-year data on 808 men who were completely compliant with the program (J. Urology 2015;193:1950-5). Restricting the cohort in this way gives a much more accurate prediction; he said up to 18% of men without disease progression will drop out of active surveillance because they find the process onerous, especially the biopsies.

For the first 2 years of follow-up, the rate of disease reclassification was nearly 0% in both low- and very low-risk groups. “But after that, there was a pretty big gap developing between the two, with the low-risk group doing worse,” Dr. Alam said. By 10 years, 60% of the very low-risk group still had no disease progression; that number remained stable throughout the remainder of the study period. Among low-risk men, however, 60% did have a disease stage reclassification by 7 years; by 10 years, nearly 80% had progressed.

Despite that, the overall risk of reclassification declined sharply over time, decreasing by 30% after every stable biopsy. “If a patient reached 7-9 years without a reclassification, his risk of disease by 15 years was virtually 0,” Dr. Alam said. “This may help reassure men and their doctors about the risks of surveillance, and also reduce the dropout rate by giving them a sense of security – a sense that we really can trust the data and make good decisions based on it.”

Neither Dr. Tosoian nor Dr. Alam had any financial disclosures.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – Long-term active surveillance seems to be a safe and effective way to avoid overtreatment in men with low- and very low-risk prostate cancer, while still offering a very good chance of catching progressive disease.

According to new data presented at the annual meeting of the American Urological Association, less than 3% of men developed metastatic disease or died from prostate cancer over 15 years of follow-up. The men’s risk of progression dramatically declined over time, decreasing by 30% after each annual, unchanged biopsy.

The findings should reassure both physicians and patients, all of whom want to balance the potential side effects of prostate cancer treatment with the risk of progressive disease, said Dr. Stacy Loeb of New York University, New York.

“Physicians in the U.S. have been slow to adopt the practice of active surveillance, which is much more common in other parts of the world,” said Dr. Loeb, who moderated the press briefing where the data were unveiled. She has worked with Swedish researchers, who determined that 84% of men with very low-risk cancers and 66% of those with low-risk cancers are being managed this way. “The question we have to ask is why we have been so slow to adopt this. Hopefully, studies like these, showing so many men free of disease even at 15 years, will encourage greater acceptance in this country.”

The briefing highlighted several studies on active surveillance; two of these were performed on the Johns Hopkins Active Surveillance Program cohort, which has enrolled about 1,300 men since 1995. Most (71%) have very low-risk cancer; the remainder have low-risk cancer.

The Hopkins protocol calls for a clinical exam and prostate specific antigen (PSA) test twice a year, annual prostate biopsy, and imaging every either year, said Dr. Jeffrey Tosoian, a urology resident at the university.

Triggers for treatment include a change in biopsy or patient decision. Changes in PSA and clinical exam alone don’t trigger treatment, but may prompt a stepped-up monitoring schedule or additional diagnostic studies.

The Hopkins cohort is a fairly typical prostate cancer group. The patients’ mean age at diagnosis is about 66 years, and their mean PSA level is 5.2 ng/mL. Mean follow-up time is now 5 years, but Dr. Tosoian also presented 10- and 15-year data.

At 5 years, 36% of the group had converted to some form of treatment. By 10 and 15 years, conversion had occurred in 50% and 56%, respectively. Not surprisingly, the rate of death from any cause increased as patients aged, from 4% by year 5, to 7% and 31% by years 10 and 15.

But the rate of prostate cancer-specific death was very low throughout the study period: 0.15% at year 5 and 1% at years 10 and 15. Over the entire 15 years, less than 1% of the men died from prostate cancer or developed metastatic disease.

These findings were somewhat more positive than those recently reported by a team at Sunnybrook University, Toronto (J. Clin. Oncol. 2015;33:272-7). That surveillance protocol is less stringent than the one at Hopkins, Dr. Tosoian said, with biopsies every 3-5 years, based on clinical findings and PSA levels.

In that cohort of 819 patients with a median follow-up of 6 years, 3% developed metastatic disease by 15 years and 1.5% died from it, but the men were nine times more likely to die from some other cause than their cancer.

“Certainly, our more intensive monitoring at Hopkins was associated with more treatment, but also with lower death and metastatic rates,” Dr. Tosoian said. “So there are still trade-offs in balancing overtreatment, but the real risk of cancer mortality is quite small.”

However, the question of how long must watchful waiting continue remains. Understandably, most men don’t want to commit to years and years of annual prostate biopsies, said Dr. Ridwan Alam, also of Johns Hopkins.

Dr. Alam presented 15-year data on 808 men who were completely compliant with the program (J. Urology 2015;193:1950-5). Restricting the cohort in this way gives a much more accurate prediction; he said up to 18% of men without disease progression will drop out of active surveillance because they find the process onerous, especially the biopsies.

For the first 2 years of follow-up, the rate of disease reclassification was nearly 0% in both low- and very low-risk groups. “But after that, there was a pretty big gap developing between the two, with the low-risk group doing worse,” Dr. Alam said. By 10 years, 60% of the very low-risk group still had no disease progression; that number remained stable throughout the remainder of the study period. Among low-risk men, however, 60% did have a disease stage reclassification by 7 years; by 10 years, nearly 80% had progressed.

Despite that, the overall risk of reclassification declined sharply over time, decreasing by 30% after every stable biopsy. “If a patient reached 7-9 years without a reclassification, his risk of disease by 15 years was virtually 0,” Dr. Alam said. “This may help reassure men and their doctors about the risks of surveillance, and also reduce the dropout rate by giving them a sense of security – a sense that we really can trust the data and make good decisions based on it.”

Neither Dr. Tosoian nor Dr. Alam had any financial disclosures.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – Long-term active surveillance seems to be a safe and effective way to avoid overtreatment in men with low- and very low-risk prostate cancer, while still offering a very good chance of catching progressive disease.

According to new data presented at the annual meeting of the American Urological Association, less than 3% of men developed metastatic disease or died from prostate cancer over 15 years of follow-up. The men’s risk of progression dramatically declined over time, decreasing by 30% after each annual, unchanged biopsy.

The findings should reassure both physicians and patients, all of whom want to balance the potential side effects of prostate cancer treatment with the risk of progressive disease, said Dr. Stacy Loeb of New York University, New York.

“Physicians in the U.S. have been slow to adopt the practice of active surveillance, which is much more common in other parts of the world,” said Dr. Loeb, who moderated the press briefing where the data were unveiled. She has worked with Swedish researchers, who determined that 84% of men with very low-risk cancers and 66% of those with low-risk cancers are being managed this way. “The question we have to ask is why we have been so slow to adopt this. Hopefully, studies like these, showing so many men free of disease even at 15 years, will encourage greater acceptance in this country.”

The briefing highlighted several studies on active surveillance; two of these were performed on the Johns Hopkins Active Surveillance Program cohort, which has enrolled about 1,300 men since 1995. Most (71%) have very low-risk cancer; the remainder have low-risk cancer.

The Hopkins protocol calls for a clinical exam and prostate specific antigen (PSA) test twice a year, annual prostate biopsy, and imaging every either year, said Dr. Jeffrey Tosoian, a urology resident at the university.

Triggers for treatment include a change in biopsy or patient decision. Changes in PSA and clinical exam alone don’t trigger treatment, but may prompt a stepped-up monitoring schedule or additional diagnostic studies.

The Hopkins cohort is a fairly typical prostate cancer group. The patients’ mean age at diagnosis is about 66 years, and their mean PSA level is 5.2 ng/mL. Mean follow-up time is now 5 years, but Dr. Tosoian also presented 10- and 15-year data.

At 5 years, 36% of the group had converted to some form of treatment. By 10 and 15 years, conversion had occurred in 50% and 56%, respectively. Not surprisingly, the rate of death from any cause increased as patients aged, from 4% by year 5, to 7% and 31% by years 10 and 15.

But the rate of prostate cancer-specific death was very low throughout the study period: 0.15% at year 5 and 1% at years 10 and 15. Over the entire 15 years, less than 1% of the men died from prostate cancer or developed metastatic disease.

These findings were somewhat more positive than those recently reported by a team at Sunnybrook University, Toronto (J. Clin. Oncol. 2015;33:272-7). That surveillance protocol is less stringent than the one at Hopkins, Dr. Tosoian said, with biopsies every 3-5 years, based on clinical findings and PSA levels.

In that cohort of 819 patients with a median follow-up of 6 years, 3% developed metastatic disease by 15 years and 1.5% died from it, but the men were nine times more likely to die from some other cause than their cancer.

“Certainly, our more intensive monitoring at Hopkins was associated with more treatment, but also with lower death and metastatic rates,” Dr. Tosoian said. “So there are still trade-offs in balancing overtreatment, but the real risk of cancer mortality is quite small.”

However, the question of how long must watchful waiting continue remains. Understandably, most men don’t want to commit to years and years of annual prostate biopsies, said Dr. Ridwan Alam, also of Johns Hopkins.

Dr. Alam presented 15-year data on 808 men who were completely compliant with the program (J. Urology 2015;193:1950-5). Restricting the cohort in this way gives a much more accurate prediction; he said up to 18% of men without disease progression will drop out of active surveillance because they find the process onerous, especially the biopsies.

For the first 2 years of follow-up, the rate of disease reclassification was nearly 0% in both low- and very low-risk groups. “But after that, there was a pretty big gap developing between the two, with the low-risk group doing worse,” Dr. Alam said. By 10 years, 60% of the very low-risk group still had no disease progression; that number remained stable throughout the remainder of the study period. Among low-risk men, however, 60% did have a disease stage reclassification by 7 years; by 10 years, nearly 80% had progressed.

Despite that, the overall risk of reclassification declined sharply over time, decreasing by 30% after every stable biopsy. “If a patient reached 7-9 years without a reclassification, his risk of disease by 15 years was virtually 0,” Dr. Alam said. “This may help reassure men and their doctors about the risks of surveillance, and also reduce the dropout rate by giving them a sense of security – a sense that we really can trust the data and make good decisions based on it.”

Neither Dr. Tosoian nor Dr. Alam had any financial disclosures.

[email protected]

On Twitter @alz_gal

WASHINGTON – The antiepileptic drug perampanel cut the frequency of primary generalized tonic-clonic seizures by 50% versus placebo in patients who were already taking a number of other anti-seizure medications in a phase III randomized trial.

Perampanel (Fycompa), a glutamate receptor blocker, was also associated with significantly higher rates of patients being seizure free or having at least a 50% response, compared with placebo, Dr. Jacqueline French reported at the annual meeting of the American Academy of Neurology.

The study randomized 164 patients to either placebo or up to 8 mg daily of perampanel. It was conducted at 78 sites in 16 countries. There was a run-in period of 4-8 weeks, followed by a month of titration, 13 weeks of maintenance therapy, and a 3-year extension phase. Of 164 patients randomized, 162 completed the entire study, said Dr. French, codirector of epilepsy research and epilepsy clinical trials at the NYU Comprehensive Epilepsy Center, New York. She is also chief scientific officer of the Epilepsy Foundation of America.

The patients were all at least 12 years old and taking up to three other antiepileptic drugs without complete seizure control. During the 8-week pre-randomization period, they had to experience at least three primary generalized tonic-clonic (PGTC) seizures.

At the end of follow-up, add-on perampanel significantly outperformed placebo in the primary measure of change in PGTC seizure frequency (median 76% vs. 38%). It also conferred a significant advantage in the percentage of patients with at least a 50% reduction in seizure frequency (64% vs. 39%). Significantly more patients in the perampanel group became seizure-free (31% vs. 12%).

The safety dataset comprised 163 patients. Most patients taking perampanel (83%) experienced some kind of drug-related adverse event. The most common were dizziness (32% vs. 6% placebo), fatigue (15% vs. 6%), and headache (12% vs. 10%). Six serious adverse events occurred in the active group and seven in the placebo group. There were two deaths, one in each group: an accidental drowning in the perampanel group and a case of sudden unexplained death in epilepsy (SUDEP) in the placebo group.

Perampanel is approved as an adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older.

Eisai Inc. sponsored the study. Dr. French has received personal compensation and research support from Eisai, as well as numerous other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – The antiepileptic drug perampanel cut the frequency of primary generalized tonic-clonic seizures by 50% versus placebo in patients who were already taking a number of other anti-seizure medications in a phase III randomized trial.

Perampanel (Fycompa), a glutamate receptor blocker, was also associated with significantly higher rates of patients being seizure free or having at least a 50% response, compared with placebo, Dr. Jacqueline French reported at the annual meeting of the American Academy of Neurology.

The study randomized 164 patients to either placebo or up to 8 mg daily of perampanel. It was conducted at 78 sites in 16 countries. There was a run-in period of 4-8 weeks, followed by a month of titration, 13 weeks of maintenance therapy, and a 3-year extension phase. Of 164 patients randomized, 162 completed the entire study, said Dr. French, codirector of epilepsy research and epilepsy clinical trials at the NYU Comprehensive Epilepsy Center, New York. She is also chief scientific officer of the Epilepsy Foundation of America.

The patients were all at least 12 years old and taking up to three other antiepileptic drugs without complete seizure control. During the 8-week pre-randomization period, they had to experience at least three primary generalized tonic-clonic (PGTC) seizures.

At the end of follow-up, add-on perampanel significantly outperformed placebo in the primary measure of change in PGTC seizure frequency (median 76% vs. 38%). It also conferred a significant advantage in the percentage of patients with at least a 50% reduction in seizure frequency (64% vs. 39%). Significantly more patients in the perampanel group became seizure-free (31% vs. 12%).

The safety dataset comprised 163 patients. Most patients taking perampanel (83%) experienced some kind of drug-related adverse event. The most common were dizziness (32% vs. 6% placebo), fatigue (15% vs. 6%), and headache (12% vs. 10%). Six serious adverse events occurred in the active group and seven in the placebo group. There were two deaths, one in each group: an accidental drowning in the perampanel group and a case of sudden unexplained death in epilepsy (SUDEP) in the placebo group.

Perampanel is approved as an adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older.

Eisai Inc. sponsored the study. Dr. French has received personal compensation and research support from Eisai, as well as numerous other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – The antiepileptic drug perampanel cut the frequency of primary generalized tonic-clonic seizures by 50% versus placebo in patients who were already taking a number of other anti-seizure medications in a phase III randomized trial.

Perampanel (Fycompa), a glutamate receptor blocker, was also associated with significantly higher rates of patients being seizure free or having at least a 50% response, compared with placebo, Dr. Jacqueline French reported at the annual meeting of the American Academy of Neurology.

The study randomized 164 patients to either placebo or up to 8 mg daily of perampanel. It was conducted at 78 sites in 16 countries. There was a run-in period of 4-8 weeks, followed by a month of titration, 13 weeks of maintenance therapy, and a 3-year extension phase. Of 164 patients randomized, 162 completed the entire study, said Dr. French, codirector of epilepsy research and epilepsy clinical trials at the NYU Comprehensive Epilepsy Center, New York. She is also chief scientific officer of the Epilepsy Foundation of America.

The patients were all at least 12 years old and taking up to three other antiepileptic drugs without complete seizure control. During the 8-week pre-randomization period, they had to experience at least three primary generalized tonic-clonic (PGTC) seizures.

At the end of follow-up, add-on perampanel significantly outperformed placebo in the primary measure of change in PGTC seizure frequency (median 76% vs. 38%). It also conferred a significant advantage in the percentage of patients with at least a 50% reduction in seizure frequency (64% vs. 39%). Significantly more patients in the perampanel group became seizure-free (31% vs. 12%).

The safety dataset comprised 163 patients. Most patients taking perampanel (83%) experienced some kind of drug-related adverse event. The most common were dizziness (32% vs. 6% placebo), fatigue (15% vs. 6%), and headache (12% vs. 10%). Six serious adverse events occurred in the active group and seven in the placebo group. There were two deaths, one in each group: an accidental drowning in the perampanel group and a case of sudden unexplained death in epilepsy (SUDEP) in the placebo group.

Perampanel is approved as an adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older.

Eisai Inc. sponsored the study. Dr. French has received personal compensation and research support from Eisai, as well as numerous other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

Men who have sex with men, and women who have sexual relations with them, will be permitted to donate blood if a year has elapsed between the last such sexual encounter and the time of donation, the Food and Drug Administration has recommended.

The agency’s draft guidance follows that of the federal Advisory Committee on Blood and Tissue Safety and Availability. In November 2014, the group voted 16-2 to support a 1-year deferral policy for these populations. Any deferral decision made at a donor site would be based on donor self-identification and self-report, the draft guidance noted. Clinicians should “use their own discretion” with regard to deferring a donation from a person who self-identifies as transgender.

The document would supplant prior guidance, issued in 1985, which recommended permanent deferral for men who have sex with men (MSM) and women who had sex with them.

Should it be adopted, the new policy “will better align the deferral period with that of other men and women at increased risk for HIV infection,” then FDA Commissioner Dr. Margaret A. Hamburg said in a press statement last December. Safety and blood surveillance measures already in place will be enough to detect any HIV-contaminated blood that might enter the donor pool, she said.

The national blood surveillance system will help the agency monitor the effect of any policy change and further ensure the continued safety of the blood supply. This, along with a donor education program, has reduced the risk of an HIV infection from donated blood to about 1/1.47 million transfusions, according to the draft document.

The proposal was based on the committee’s evidence review, during which data from a similar change in deferral status in Australia weighed in favor of the recommendations. During the 5 years before and after a change from lifetime deferral to the 1-year deferral for MSM, there was no change in the risk of HIV-contaminated blood entering the donor pool or the proportion of HIV-positive donors.

Despite being “a step in the right direction,” the proposed 1-year deferral still discriminates against MSM, according to David Stacy, government affairs director for the Human Rights Campaign, the nation’s largest lesbian, gay, bisexual, and transgender civil rights organization.

“This policy prevents men from donating life-saving blood based solely on their sexual orientation rather than actual risk to the blood supply,” he said in a press statement. “It simply cannot be justified in light of current scientific research and updated blood screening technology.”

The draft guidance is not binding. It will be published on the Federal Register, which at that time will announce the deadline for comment.

[email protected]

On Twitter @alz_gal

Men who have sex with men, and women who have sexual relations with them, will be permitted to donate blood if a year has elapsed between the last such sexual encounter and the time of donation, the Food and Drug Administration has recommended.

The agency’s draft guidance follows that of the federal Advisory Committee on Blood and Tissue Safety and Availability. In November 2014, the group voted 16-2 to support a 1-year deferral policy for these populations. Any deferral decision made at a donor site would be based on donor self-identification and self-report, the draft guidance noted. Clinicians should “use their own discretion” with regard to deferring a donation from a person who self-identifies as transgender.

The document would supplant prior guidance, issued in 1985, which recommended permanent deferral for men who have sex with men (MSM) and women who had sex with them.

Should it be adopted, the new policy “will better align the deferral period with that of other men and women at increased risk for HIV infection,” then FDA Commissioner Dr. Margaret A. Hamburg said in a press statement last December. Safety and blood surveillance measures already in place will be enough to detect any HIV-contaminated blood that might enter the donor pool, she said.

The national blood surveillance system will help the agency monitor the effect of any policy change and further ensure the continued safety of the blood supply. This, along with a donor education program, has reduced the risk of an HIV infection from donated blood to about 1/1.47 million transfusions, according to the draft document.

The proposal was based on the committee’s evidence review, during which data from a similar change in deferral status in Australia weighed in favor of the recommendations. During the 5 years before and after a change from lifetime deferral to the 1-year deferral for MSM, there was no change in the risk of HIV-contaminated blood entering the donor pool or the proportion of HIV-positive donors.

Despite being “a step in the right direction,” the proposed 1-year deferral still discriminates against MSM, according to David Stacy, government affairs director for the Human Rights Campaign, the nation’s largest lesbian, gay, bisexual, and transgender civil rights organization.

“This policy prevents men from donating life-saving blood based solely on their sexual orientation rather than actual risk to the blood supply,” he said in a press statement. “It simply cannot be justified in light of current scientific research and updated blood screening technology.”

The draft guidance is not binding. It will be published on the Federal Register, which at that time will announce the deadline for comment.

[email protected]

On Twitter @alz_gal

Men who have sex with men, and women who have sexual relations with them, will be permitted to donate blood if a year has elapsed between the last such sexual encounter and the time of donation, the Food and Drug Administration has recommended.

The agency’s draft guidance follows that of the federal Advisory Committee on Blood and Tissue Safety and Availability. In November 2014, the group voted 16-2 to support a 1-year deferral policy for these populations. Any deferral decision made at a donor site would be based on donor self-identification and self-report, the draft guidance noted. Clinicians should “use their own discretion” with regard to deferring a donation from a person who self-identifies as transgender.

The document would supplant prior guidance, issued in 1985, which recommended permanent deferral for men who have sex with men (MSM) and women who had sex with them.

Should it be adopted, the new policy “will better align the deferral period with that of other men and women at increased risk for HIV infection,” then FDA Commissioner Dr. Margaret A. Hamburg said in a press statement last December. Safety and blood surveillance measures already in place will be enough to detect any HIV-contaminated blood that might enter the donor pool, she said.

The national blood surveillance system will help the agency monitor the effect of any policy change and further ensure the continued safety of the blood supply. This, along with a donor education program, has reduced the risk of an HIV infection from donated blood to about 1/1.47 million transfusions, according to the draft document.

The proposal was based on the committee’s evidence review, during which data from a similar change in deferral status in Australia weighed in favor of the recommendations. During the 5 years before and after a change from lifetime deferral to the 1-year deferral for MSM, there was no change in the risk of HIV-contaminated blood entering the donor pool or the proportion of HIV-positive donors.

Despite being “a step in the right direction,” the proposed 1-year deferral still discriminates against MSM, according to David Stacy, government affairs director for the Human Rights Campaign, the nation’s largest lesbian, gay, bisexual, and transgender civil rights organization.

“This policy prevents men from donating life-saving blood based solely on their sexual orientation rather than actual risk to the blood supply,” he said in a press statement. “It simply cannot be justified in light of current scientific research and updated blood screening technology.”

The draft guidance is not binding. It will be published on the Federal Register, which at that time will announce the deadline for comment.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease ... These can be very challenging patients with multiple comorbidities,” treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said.

“We may classify some of these – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “They are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated, and impose unnecessary risks, including falls, seizures, worsened Parkinsonism, and even death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease ... These can be very challenging patients with multiple comorbidities,” treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said.

“We may classify some of these – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “They are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated, and impose unnecessary risks, including falls, seizures, worsened Parkinsonism, and even death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease ... These can be very challenging patients with multiple comorbidities,” treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said.

“We may classify some of these – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “They are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated, and impose unnecessary risks, including falls, seizures, worsened Parkinsonism, and even death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

[email protected]

On Twitter @alz_gal