Bruce Jancin

WASHINGTON – Apixaban yields the great medical cost savings of the three novel oral anticoagulants available as alternatives to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation, according to a new comparative analysis.

This analysis differed from prior cost savings studies, which relied upon relative risk reductions for stroke and major bleeding events obtained directly from the pivotal phase III clinical trials conducted for each of the novel oral anticoagulants (NOACs).

Instead, the new analysis used as the comparator arm real-world event rates in warfarin-treated patients in a large national health insurance claims database. This was done because of the high likelihood that event rates in warfarin-treated controls in the clinical trials may be considerably lower than in everyday practice, since the trials were carried out in a selected patient population, with exclusion of the elderly and others at higher risk of adverse events, Michael Stokes explained at the annual meeting of the American College of Cardiology.

The investigators used the 21% relative risk reductions for both stroke and major bleeding with the use of apixaban (Eliquis), compared with warfarin in the ARISTOTLE trial (N. Engl. J. Med. 2011;365:981-92), and applied those relative risk reductions to 23,525 managed care patients with atrial fibrillation on warfarin for stroke prevention in the Medco claims database. They found that the use of apixaban instead of warfarin would result in an estimated 1.1 fewer strokes and 2.1 fewer major bleeding events excluding intracranial hemorrhage per 100 person-years of follow-up in a real-world population, said Mr. Stokes of Evidera, a health care consulting firm in Montreal.

In contrast, applying the relative risk figures for dabigatran (Pradaxa) obtained from the RE-LY trial (N. Engl. J. Med. 2009;361:1139-51) yielded estimates of 1.9 fewer strokes but 0.7 additional major bleeding events per 100 person-years, compared with warfarin in everyday practice. For rivaroxaban (Xarelto), the data from the ROCKET-AF trial (N. Engl. J. Med. 2011;365:883-91) pointed to 0.8 fewer strokes than with warfarin, but 1.4 more major bleeding events, he continued.

For the key outcome of total medical costs saved through avoidance of stroke or major bleeding through the use of a NOAC rather than warfarin, the estimates were $1,245/year for a patient on apixaban and $555 for dabigatran. In contrast, rivaroxaban was not associated with a savings, but rather with an increase in medical costs of $144 per patient per year.

These are figures that take some of the sting out of the high prescription costs for the NOACs. The savings estimates relied upon incremental 1-year medical cost figures of $44,792/stroke and $35,829/major bleeding event, excluding intracranial hemorrhage, which were obtained from another study (Stroke 2011;42:112-8).

Since patients on warfarin for stroke prevention in the Medco database were older and thus higher risk than those in the NOAC pivotal trials were, the total medical cost savings for each NOAC were larger in the new analysis. In one earlier analysis that relied upon reference rates from the clinical trials, the total medical cost savings estimate for each NOAC, compared with warfarin, was $485 per patient per year for apixaban, $179 for dabigatran, and $89 for rivaroxaban (J. Med. Econ. 2012;15:776-85).

Mr. Stokes’s analysis was carried out by Evidera with research funding from Bristol-Myers Squibb and Pfizer, which jointly developed apixaban.

bjancin@frontlinemedcom.com

WASHINGTON – Apixaban yields the great medical cost savings of the three novel oral anticoagulants available as alternatives to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation, according to a new comparative analysis.

This analysis differed from prior cost savings studies, which relied upon relative risk reductions for stroke and major bleeding events obtained directly from the pivotal phase III clinical trials conducted for each of the novel oral anticoagulants (NOACs).

Instead, the new analysis used as the comparator arm real-world event rates in warfarin-treated patients in a large national health insurance claims database. This was done because of the high likelihood that event rates in warfarin-treated controls in the clinical trials may be considerably lower than in everyday practice, since the trials were carried out in a selected patient population, with exclusion of the elderly and others at higher risk of adverse events, Michael Stokes explained at the annual meeting of the American College of Cardiology.

The investigators used the 21% relative risk reductions for both stroke and major bleeding with the use of apixaban (Eliquis), compared with warfarin in the ARISTOTLE trial (N. Engl. J. Med. 2011;365:981-92), and applied those relative risk reductions to 23,525 managed care patients with atrial fibrillation on warfarin for stroke prevention in the Medco claims database. They found that the use of apixaban instead of warfarin would result in an estimated 1.1 fewer strokes and 2.1 fewer major bleeding events excluding intracranial hemorrhage per 100 person-years of follow-up in a real-world population, said Mr. Stokes of Evidera, a health care consulting firm in Montreal.

In contrast, applying the relative risk figures for dabigatran (Pradaxa) obtained from the RE-LY trial (N. Engl. J. Med. 2009;361:1139-51) yielded estimates of 1.9 fewer strokes but 0.7 additional major bleeding events per 100 person-years, compared with warfarin in everyday practice. For rivaroxaban (Xarelto), the data from the ROCKET-AF trial (N. Engl. J. Med. 2011;365:883-91) pointed to 0.8 fewer strokes than with warfarin, but 1.4 more major bleeding events, he continued.

For the key outcome of total medical costs saved through avoidance of stroke or major bleeding through the use of a NOAC rather than warfarin, the estimates were $1,245/year for a patient on apixaban and $555 for dabigatran. In contrast, rivaroxaban was not associated with a savings, but rather with an increase in medical costs of $144 per patient per year.

These are figures that take some of the sting out of the high prescription costs for the NOACs. The savings estimates relied upon incremental 1-year medical cost figures of $44,792/stroke and $35,829/major bleeding event, excluding intracranial hemorrhage, which were obtained from another study (Stroke 2011;42:112-8).

Since patients on warfarin for stroke prevention in the Medco database were older and thus higher risk than those in the NOAC pivotal trials were, the total medical cost savings for each NOAC were larger in the new analysis. In one earlier analysis that relied upon reference rates from the clinical trials, the total medical cost savings estimate for each NOAC, compared with warfarin, was $485 per patient per year for apixaban, $179 for dabigatran, and $89 for rivaroxaban (J. Med. Econ. 2012;15:776-85).

Mr. Stokes’s analysis was carried out by Evidera with research funding from Bristol-Myers Squibb and Pfizer, which jointly developed apixaban.

bjancin@frontlinemedcom.com

WASHINGTON – Apixaban yields the great medical cost savings of the three novel oral anticoagulants available as alternatives to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation, according to a new comparative analysis.

This analysis differed from prior cost savings studies, which relied upon relative risk reductions for stroke and major bleeding events obtained directly from the pivotal phase III clinical trials conducted for each of the novel oral anticoagulants (NOACs).

Instead, the new analysis used as the comparator arm real-world event rates in warfarin-treated patients in a large national health insurance claims database. This was done because of the high likelihood that event rates in warfarin-treated controls in the clinical trials may be considerably lower than in everyday practice, since the trials were carried out in a selected patient population, with exclusion of the elderly and others at higher risk of adverse events, Michael Stokes explained at the annual meeting of the American College of Cardiology.

The investigators used the 21% relative risk reductions for both stroke and major bleeding with the use of apixaban (Eliquis), compared with warfarin in the ARISTOTLE trial (N. Engl. J. Med. 2011;365:981-92), and applied those relative risk reductions to 23,525 managed care patients with atrial fibrillation on warfarin for stroke prevention in the Medco claims database. They found that the use of apixaban instead of warfarin would result in an estimated 1.1 fewer strokes and 2.1 fewer major bleeding events excluding intracranial hemorrhage per 100 person-years of follow-up in a real-world population, said Mr. Stokes of Evidera, a health care consulting firm in Montreal.

In contrast, applying the relative risk figures for dabigatran (Pradaxa) obtained from the RE-LY trial (N. Engl. J. Med. 2009;361:1139-51) yielded estimates of 1.9 fewer strokes but 0.7 additional major bleeding events per 100 person-years, compared with warfarin in everyday practice. For rivaroxaban (Xarelto), the data from the ROCKET-AF trial (N. Engl. J. Med. 2011;365:883-91) pointed to 0.8 fewer strokes than with warfarin, but 1.4 more major bleeding events, he continued.

For the key outcome of total medical costs saved through avoidance of stroke or major bleeding through the use of a NOAC rather than warfarin, the estimates were $1,245/year for a patient on apixaban and $555 for dabigatran. In contrast, rivaroxaban was not associated with a savings, but rather with an increase in medical costs of $144 per patient per year.

These are figures that take some of the sting out of the high prescription costs for the NOACs. The savings estimates relied upon incremental 1-year medical cost figures of $44,792/stroke and $35,829/major bleeding event, excluding intracranial hemorrhage, which were obtained from another study (Stroke 2011;42:112-8).

Since patients on warfarin for stroke prevention in the Medco database were older and thus higher risk than those in the NOAC pivotal trials were, the total medical cost savings for each NOAC were larger in the new analysis. In one earlier analysis that relied upon reference rates from the clinical trials, the total medical cost savings estimate for each NOAC, compared with warfarin, was $485 per patient per year for apixaban, $179 for dabigatran, and $89 for rivaroxaban (J. Med. Econ. 2012;15:776-85).

Mr. Stokes’s analysis was carried out by Evidera with research funding from Bristol-Myers Squibb and Pfizer, which jointly developed apixaban.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Guttate psoriasis in children warrants more aggressive monitoring and treatment in an effort to head off more severe disease later, according to Dr. Wynnis L. Tom.

Pediatric psoriasis presenting initially as guttate disease is more likely to progress to severe psoriasis prior to adulthood than if the initial presentation took the form of plaque psoriasis, according to data from a multicenter U.S. study of the clinical manifestations of pediatric psoriasis.

The cross-sectional study included 181 children aged 5-17 years with plaque psoriasis, and the results highlighted important differences between childhood-onset and adult-onset disease, Dr. Tom said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

About 40% of cases of pediatric psoriasis that presented initially as guttate psoriasis progressed to chronic disease. That was not a higher proportion than in children whose initial disease was plaque psoriasis, said Dr. Tom of the University of California, San Diego, and Rady Children’s Hospital. However, 36% of youths with severe psoriasis had a history of disease onset with guttate morphology compared with 22% of those with mild disease, she said.

The peak severity of psoriasis was defined historically as either mild or severe based upon body surface area involvement and Physician Global Assessment.

Overall, 79% of study participants had a history of scalp psoriasis and 39% had a history of nail involvement. However, these disease expressions were unrelated to psoriasis severity.

Boys were three times more likely than girls to have had nail involvement, but 60% less likely to have a history of scalp involvement. These sex-related differences probably reflect koebnerization, Dr. Tom said.

Approximately 5% of the patients had psoriasis restricted to their face alone. Among those with body involvement, the face was included in nearly half of cases.

Session chair Dr. Lawrence F. Eichenfield praised this study (Pediatr. Dermatol. 2013;30:424-8), on which Dr. Tom was a coauthor, as one of the top articles in the field of pediatric dermatology published within the past year. Although various studies indicate that 27%-45% of all cases of psoriasis begin in childhood, the clinical aspects of pediatric psoriasis haven’t been well characterized until now, said Dr. Eichenfield, professor of clinical pediatrics and medicine and chief of pediatric and adolescent dermatology at the University of California, San Diego.

Dr. Eichenfield also singled out Dr. Tom as coauthor of yet another of his top picks of recently published studies on the topic of pediatric psoriasis. This cross-sectional study included 409 psoriasis patients aged 5-17 years in nine countries. The prevalence of excess adiposity as defined by a body mass index at the 85th percentile or greater was 38% among the psoriatic children compared with 21% in matched controls. The likelihood of obesity as defined by a BMI in the 95th percentile or higher was 4.9-fold greater in children with severe psoriasis than in controls, and 3.6-fold greater in those with mild psoriasis compared than in controls. Among U.S. patients, the psoriasis/obesity association was magnified such that American children with severe and mild psoriasis were respectively 7.6-fold and 4.7-fold more likely to be obese than controls (JAMA Dermatol. 2013;149:166-76).

Central adiposity – an element of metabolic syndrome associated with increased cardiovascular risk in adults – was present as defined by waist circumference greater than the 90th percentile in 21% of youths with severe psoriasis, 14% with mild disease, and 9% of controls. In U.S. participants, these figures ballooned to 31%, 21%, and 12%, respectively.

Dr. Tom cited evidence from yet another study in which she was a coinvestigator suggesting that obesity may be a risk factor for pediatric psoriasis, rather than the other way around. In this three-center study, nearly all of a group of pediatric psoriasis patients were overweight or obese for at least 2 years prior to their psoriasis onset.

Current National Psoriasis Foundation guidelines recommend initiating cardiovascular risk factor screening "as early as age 20." Dr. Tom is among those seeking to revise the guidelines to extend screening to pediatric psoriasis patients. She said she now recommends consideration of cardiovascular screening in overweight and obese pediatric psoriasis patients – including monitoring of blood pressure, lipids, fasting blood glucose, and liver enzymes – along with hard-hitting guidance on dietary modifications, weight loss, and the importance of exercise.

"Ongoing studies are assessing the need for screening labs for nonoverweight children with psoriasis. Hopefully this will be sorted out soon as a group in our field. We’re hoping for updated guidelines," she said.

Dr. Tom disclosed serving as a financially uncompensated investigator for Amgen and Anacor.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Guttate psoriasis in children warrants more aggressive monitoring and treatment in an effort to head off more severe disease later, according to Dr. Wynnis L. Tom.

Pediatric psoriasis presenting initially as guttate disease is more likely to progress to severe psoriasis prior to adulthood than if the initial presentation took the form of plaque psoriasis, according to data from a multicenter U.S. study of the clinical manifestations of pediatric psoriasis.

The cross-sectional study included 181 children aged 5-17 years with plaque psoriasis, and the results highlighted important differences between childhood-onset and adult-onset disease, Dr. Tom said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

About 40% of cases of pediatric psoriasis that presented initially as guttate psoriasis progressed to chronic disease. That was not a higher proportion than in children whose initial disease was plaque psoriasis, said Dr. Tom of the University of California, San Diego, and Rady Children’s Hospital. However, 36% of youths with severe psoriasis had a history of disease onset with guttate morphology compared with 22% of those with mild disease, she said.

The peak severity of psoriasis was defined historically as either mild or severe based upon body surface area involvement and Physician Global Assessment.

Overall, 79% of study participants had a history of scalp psoriasis and 39% had a history of nail involvement. However, these disease expressions were unrelated to psoriasis severity.

Boys were three times more likely than girls to have had nail involvement, but 60% less likely to have a history of scalp involvement. These sex-related differences probably reflect koebnerization, Dr. Tom said.

Approximately 5% of the patients had psoriasis restricted to their face alone. Among those with body involvement, the face was included in nearly half of cases.

Session chair Dr. Lawrence F. Eichenfield praised this study (Pediatr. Dermatol. 2013;30:424-8), on which Dr. Tom was a coauthor, as one of the top articles in the field of pediatric dermatology published within the past year. Although various studies indicate that 27%-45% of all cases of psoriasis begin in childhood, the clinical aspects of pediatric psoriasis haven’t been well characterized until now, said Dr. Eichenfield, professor of clinical pediatrics and medicine and chief of pediatric and adolescent dermatology at the University of California, San Diego.

Dr. Eichenfield also singled out Dr. Tom as coauthor of yet another of his top picks of recently published studies on the topic of pediatric psoriasis. This cross-sectional study included 409 psoriasis patients aged 5-17 years in nine countries. The prevalence of excess adiposity as defined by a body mass index at the 85th percentile or greater was 38% among the psoriatic children compared with 21% in matched controls. The likelihood of obesity as defined by a BMI in the 95th percentile or higher was 4.9-fold greater in children with severe psoriasis than in controls, and 3.6-fold greater in those with mild psoriasis compared than in controls. Among U.S. patients, the psoriasis/obesity association was magnified such that American children with severe and mild psoriasis were respectively 7.6-fold and 4.7-fold more likely to be obese than controls (JAMA Dermatol. 2013;149:166-76).

Central adiposity – an element of metabolic syndrome associated with increased cardiovascular risk in adults – was present as defined by waist circumference greater than the 90th percentile in 21% of youths with severe psoriasis, 14% with mild disease, and 9% of controls. In U.S. participants, these figures ballooned to 31%, 21%, and 12%, respectively.

Dr. Tom cited evidence from yet another study in which she was a coinvestigator suggesting that obesity may be a risk factor for pediatric psoriasis, rather than the other way around. In this three-center study, nearly all of a group of pediatric psoriasis patients were overweight or obese for at least 2 years prior to their psoriasis onset.

Current National Psoriasis Foundation guidelines recommend initiating cardiovascular risk factor screening "as early as age 20." Dr. Tom is among those seeking to revise the guidelines to extend screening to pediatric psoriasis patients. She said she now recommends consideration of cardiovascular screening in overweight and obese pediatric psoriasis patients – including monitoring of blood pressure, lipids, fasting blood glucose, and liver enzymes – along with hard-hitting guidance on dietary modifications, weight loss, and the importance of exercise.

"Ongoing studies are assessing the need for screening labs for nonoverweight children with psoriasis. Hopefully this will be sorted out soon as a group in our field. We’re hoping for updated guidelines," she said.

Dr. Tom disclosed serving as a financially uncompensated investigator for Amgen and Anacor.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Guttate psoriasis in children warrants more aggressive monitoring and treatment in an effort to head off more severe disease later, according to Dr. Wynnis L. Tom.

Pediatric psoriasis presenting initially as guttate disease is more likely to progress to severe psoriasis prior to adulthood than if the initial presentation took the form of plaque psoriasis, according to data from a multicenter U.S. study of the clinical manifestations of pediatric psoriasis.

The cross-sectional study included 181 children aged 5-17 years with plaque psoriasis, and the results highlighted important differences between childhood-onset and adult-onset disease, Dr. Tom said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

About 40% of cases of pediatric psoriasis that presented initially as guttate psoriasis progressed to chronic disease. That was not a higher proportion than in children whose initial disease was plaque psoriasis, said Dr. Tom of the University of California, San Diego, and Rady Children’s Hospital. However, 36% of youths with severe psoriasis had a history of disease onset with guttate morphology compared with 22% of those with mild disease, she said.

The peak severity of psoriasis was defined historically as either mild or severe based upon body surface area involvement and Physician Global Assessment.

Overall, 79% of study participants had a history of scalp psoriasis and 39% had a history of nail involvement. However, these disease expressions were unrelated to psoriasis severity.

Boys were three times more likely than girls to have had nail involvement, but 60% less likely to have a history of scalp involvement. These sex-related differences probably reflect koebnerization, Dr. Tom said.

Approximately 5% of the patients had psoriasis restricted to their face alone. Among those with body involvement, the face was included in nearly half of cases.

Session chair Dr. Lawrence F. Eichenfield praised this study (Pediatr. Dermatol. 2013;30:424-8), on which Dr. Tom was a coauthor, as one of the top articles in the field of pediatric dermatology published within the past year. Although various studies indicate that 27%-45% of all cases of psoriasis begin in childhood, the clinical aspects of pediatric psoriasis haven’t been well characterized until now, said Dr. Eichenfield, professor of clinical pediatrics and medicine and chief of pediatric and adolescent dermatology at the University of California, San Diego.

Dr. Eichenfield also singled out Dr. Tom as coauthor of yet another of his top picks of recently published studies on the topic of pediatric psoriasis. This cross-sectional study included 409 psoriasis patients aged 5-17 years in nine countries. The prevalence of excess adiposity as defined by a body mass index at the 85th percentile or greater was 38% among the psoriatic children compared with 21% in matched controls. The likelihood of obesity as defined by a BMI in the 95th percentile or higher was 4.9-fold greater in children with severe psoriasis than in controls, and 3.6-fold greater in those with mild psoriasis compared than in controls. Among U.S. patients, the psoriasis/obesity association was magnified such that American children with severe and mild psoriasis were respectively 7.6-fold and 4.7-fold more likely to be obese than controls (JAMA Dermatol. 2013;149:166-76).

Central adiposity – an element of metabolic syndrome associated with increased cardiovascular risk in adults – was present as defined by waist circumference greater than the 90th percentile in 21% of youths with severe psoriasis, 14% with mild disease, and 9% of controls. In U.S. participants, these figures ballooned to 31%, 21%, and 12%, respectively.

Dr. Tom cited evidence from yet another study in which she was a coinvestigator suggesting that obesity may be a risk factor for pediatric psoriasis, rather than the other way around. In this three-center study, nearly all of a group of pediatric psoriasis patients were overweight or obese for at least 2 years prior to their psoriasis onset.

Current National Psoriasis Foundation guidelines recommend initiating cardiovascular risk factor screening "as early as age 20." Dr. Tom is among those seeking to revise the guidelines to extend screening to pediatric psoriasis patients. She said she now recommends consideration of cardiovascular screening in overweight and obese pediatric psoriasis patients – including monitoring of blood pressure, lipids, fasting blood glucose, and liver enzymes – along with hard-hitting guidance on dietary modifications, weight loss, and the importance of exercise.

"Ongoing studies are assessing the need for screening labs for nonoverweight children with psoriasis. Hopefully this will be sorted out soon as a group in our field. We’re hoping for updated guidelines," she said.

Dr. Tom disclosed serving as a financially uncompensated investigator for Amgen and Anacor.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

ORLANDO – Quality of life is not static in older persons with early-onset schizophrenia, according to a prospective longitudinal study.

"What’s presented in the literature is that you reach an end stage in late-life schizophrenia, sometimes called the quiescent state, where nothing changes. Wrong! So get that out of your head. Our work and other recent studies suggest that symptoms fluctuate. Cognitive functioning fluctuates. Mood fluctuates. And quality of life and social functioning fluctuate. Our model suggests that there remain potential opportunities to impact quality of life among older adults with schizophrenia," Dr. Carl I. Cohen declared at the annual meeting of the American Association for Geriatric Psychiatry.

He presented a prospective study of 104 community-dwelling New Yorkers with schizophrenia diagnosed before age 45. They, along with 113 matched controls, were followed for a mean of 52 months starting at an average age of 61 years.

The primary outcome in this analysis was change in the Quality of Life Index (QLI), which scores four domains – health and functioning, socioeconomics, family, and psychological/spiritual life – on a 0-30 scale.

Over the course of 52 months, the mean QLI in the schizophrenia group barely budged, moving from 22.2 to 22.6. But that bland statistic hides some fascinating changes, Dr. Cohen noted. While 24% of those in the schizophrenia group experienced a significant decline in quality of life as reflected in a drop of 2.65 points or more on the QLI, which is one-half of a standard deviation, an additional 32% had a significant improvement in QLI score. Thus, nearly three-fifths of those in the schizophrenia group had more than a half standard deviation change in their QLI scores.

Moreover, 13% of the schizophrenia group had a low baseline quality of life based upon a QLI score below the mean for the control group of matched peers, but a high QLI score at follow-up. Conversely, 15% went from a high baseline QLI to a low quality of life score at follow-up, according to Dr. Cohen, professor of psychiatry and director of the division of geriatric psychiatry at SUNY (State University of New York) Downstate Medical Center, Brooklyn.

In a multivariate analysis, several predictors of a high QLI score at follow-up emerged: fewer depressive symptoms, a higher baseline QLI, and – in a novel finding – higher religiousness scores.

"This highlights the role that religious and spiritual beliefs and activities play in this population of older adults with schizophrenia," he observed.

Also, subjects who showed improvement in their QLI score over time experienced improvement in positive symptoms of schizophrenia. "Thus, enhancing quality of life has a direct clinical impact," Dr. Cohen continued.

Audience members congratulated him for shining light on an understudied population that’s often assumed to be totally burned out.

"I’ve always said the secret of schizophrenia is not so much the young people," Dr. Cohen replied, "but actually to understand the older patients who’ve gone through the illness in its different manifestations and to see how they’ve handled it. Many of them do improve in later life, and we can learn quite a bit."

The study was funded by the National Institute of General Medical Sciences. Dr. Cohen reported having no financial disclosures, although he added, "when I speak to an audience of psychiatrists, I always feel I ought to disclose something."

bjancin@frontlinemedcom.com

ORLANDO – Quality of life is not static in older persons with early-onset schizophrenia, according to a prospective longitudinal study.

"What’s presented in the literature is that you reach an end stage in late-life schizophrenia, sometimes called the quiescent state, where nothing changes. Wrong! So get that out of your head. Our work and other recent studies suggest that symptoms fluctuate. Cognitive functioning fluctuates. Mood fluctuates. And quality of life and social functioning fluctuate. Our model suggests that there remain potential opportunities to impact quality of life among older adults with schizophrenia," Dr. Carl I. Cohen declared at the annual meeting of the American Association for Geriatric Psychiatry.

He presented a prospective study of 104 community-dwelling New Yorkers with schizophrenia diagnosed before age 45. They, along with 113 matched controls, were followed for a mean of 52 months starting at an average age of 61 years.

The primary outcome in this analysis was change in the Quality of Life Index (QLI), which scores four domains – health and functioning, socioeconomics, family, and psychological/spiritual life – on a 0-30 scale.

Over the course of 52 months, the mean QLI in the schizophrenia group barely budged, moving from 22.2 to 22.6. But that bland statistic hides some fascinating changes, Dr. Cohen noted. While 24% of those in the schizophrenia group experienced a significant decline in quality of life as reflected in a drop of 2.65 points or more on the QLI, which is one-half of a standard deviation, an additional 32% had a significant improvement in QLI score. Thus, nearly three-fifths of those in the schizophrenia group had more than a half standard deviation change in their QLI scores.

Moreover, 13% of the schizophrenia group had a low baseline quality of life based upon a QLI score below the mean for the control group of matched peers, but a high QLI score at follow-up. Conversely, 15% went from a high baseline QLI to a low quality of life score at follow-up, according to Dr. Cohen, professor of psychiatry and director of the division of geriatric psychiatry at SUNY (State University of New York) Downstate Medical Center, Brooklyn.

In a multivariate analysis, several predictors of a high QLI score at follow-up emerged: fewer depressive symptoms, a higher baseline QLI, and – in a novel finding – higher religiousness scores.

"This highlights the role that religious and spiritual beliefs and activities play in this population of older adults with schizophrenia," he observed.

Also, subjects who showed improvement in their QLI score over time experienced improvement in positive symptoms of schizophrenia. "Thus, enhancing quality of life has a direct clinical impact," Dr. Cohen continued.

Audience members congratulated him for shining light on an understudied population that’s often assumed to be totally burned out.

"I’ve always said the secret of schizophrenia is not so much the young people," Dr. Cohen replied, "but actually to understand the older patients who’ve gone through the illness in its different manifestations and to see how they’ve handled it. Many of them do improve in later life, and we can learn quite a bit."

The study was funded by the National Institute of General Medical Sciences. Dr. Cohen reported having no financial disclosures, although he added, "when I speak to an audience of psychiatrists, I always feel I ought to disclose something."

bjancin@frontlinemedcom.com

ORLANDO – Quality of life is not static in older persons with early-onset schizophrenia, according to a prospective longitudinal study.

"What’s presented in the literature is that you reach an end stage in late-life schizophrenia, sometimes called the quiescent state, where nothing changes. Wrong! So get that out of your head. Our work and other recent studies suggest that symptoms fluctuate. Cognitive functioning fluctuates. Mood fluctuates. And quality of life and social functioning fluctuate. Our model suggests that there remain potential opportunities to impact quality of life among older adults with schizophrenia," Dr. Carl I. Cohen declared at the annual meeting of the American Association for Geriatric Psychiatry.

He presented a prospective study of 104 community-dwelling New Yorkers with schizophrenia diagnosed before age 45. They, along with 113 matched controls, were followed for a mean of 52 months starting at an average age of 61 years.

The primary outcome in this analysis was change in the Quality of Life Index (QLI), which scores four domains – health and functioning, socioeconomics, family, and psychological/spiritual life – on a 0-30 scale.

Over the course of 52 months, the mean QLI in the schizophrenia group barely budged, moving from 22.2 to 22.6. But that bland statistic hides some fascinating changes, Dr. Cohen noted. While 24% of those in the schizophrenia group experienced a significant decline in quality of life as reflected in a drop of 2.65 points or more on the QLI, which is one-half of a standard deviation, an additional 32% had a significant improvement in QLI score. Thus, nearly three-fifths of those in the schizophrenia group had more than a half standard deviation change in their QLI scores.

Moreover, 13% of the schizophrenia group had a low baseline quality of life based upon a QLI score below the mean for the control group of matched peers, but a high QLI score at follow-up. Conversely, 15% went from a high baseline QLI to a low quality of life score at follow-up, according to Dr. Cohen, professor of psychiatry and director of the division of geriatric psychiatry at SUNY (State University of New York) Downstate Medical Center, Brooklyn.

In a multivariate analysis, several predictors of a high QLI score at follow-up emerged: fewer depressive symptoms, a higher baseline QLI, and – in a novel finding – higher religiousness scores.

"This highlights the role that religious and spiritual beliefs and activities play in this population of older adults with schizophrenia," he observed.

Also, subjects who showed improvement in their QLI score over time experienced improvement in positive symptoms of schizophrenia. "Thus, enhancing quality of life has a direct clinical impact," Dr. Cohen continued.

Audience members congratulated him for shining light on an understudied population that’s often assumed to be totally burned out.

"I’ve always said the secret of schizophrenia is not so much the young people," Dr. Cohen replied, "but actually to understand the older patients who’ve gone through the illness in its different manifestations and to see how they’ve handled it. Many of them do improve in later life, and we can learn quite a bit."

The study was funded by the National Institute of General Medical Sciences. Dr. Cohen reported having no financial disclosures, although he added, "when I speak to an audience of psychiatrists, I always feel I ought to disclose something."

bjancin@frontlinemedcom.com

ORLANDO – Right unilateral electroconvulsive therapy at six times the seizure threshold is markedly more effective in severely depressed patients aged 60 and older than in those who are younger, according to a multicenter randomized trial.

Bitemporal and right unilateral (RUL) ECT proved similarly effective in older patients, and both were better than bifrontal ECT in the elderly.

"One implication of our study is that in an older patient who didn’t want bitemporal ECT or whose family didn’t, then I would choose right unilateral because it’s just as good," Dr. Sohag N. Sanghani said at the annual meeting of the American Association for Geriatric Psychiatry.

He presented a secondary analysis of a double-blind multicenter trial in which 230 patients with a major unipolar or bipolar depressive episode and a mean baseline score of 35 on the 24-item Hamilton Rating Scale for Depression were randomized to one of the three ECT electrode placements. Remission rates and adverse cognitive effects were similar in all three groups, as previously shown in the primary analysis (Br. J. Psychiatry 2010;196:226-34).

Bruce Jancin/Frontline Medical News

The secondary analysis was aimed at learning if age had a differential effect upon the effectiveness of the three electrode placements. It did: RUL had a 70.4% remission rate in patients aged 60 and older, compared with 46% in the younger group. And bifrontal ECT had a 50% remission rate in older patients versus a 64.4% rate in those younger than age 60, reported Dr. Sanghani, a geriatric psychiatry fellow at Zucker Hillside Hospital in Glen Oaks, N.Y.

In contrast, the 75% remission rate with bitemporal ECT in the older group was not significantly different from the 58.3% rate in younger patients, he added.

Dr. Sanghani’s coinvestigator Dr. Georgios Petrides offered two possible explanations for the differential efficacy with age. One is that because the brain shrinks with advancing age, bifrontal electrode placement in the elderly might result in weak contact and loss of much of the stimulus, while ECT delivered via RUL placement captures much more of the brain.

"On the other hand, we always get a better response with ECT in the elderly than with younger people. So maybe depression in the elderly is a different animal than in younger people," suggested Dr. Petrides, a psychiatrist at Hofstra North Shore-LIJ School of Medicine, Glen Oaks.

Their study was funded by the National Institute of Mental Health. They reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

ORLANDO – Right unilateral electroconvulsive therapy at six times the seizure threshold is markedly more effective in severely depressed patients aged 60 and older than in those who are younger, according to a multicenter randomized trial.

Bitemporal and right unilateral (RUL) ECT proved similarly effective in older patients, and both were better than bifrontal ECT in the elderly.

"One implication of our study is that in an older patient who didn’t want bitemporal ECT or whose family didn’t, then I would choose right unilateral because it’s just as good," Dr. Sohag N. Sanghani said at the annual meeting of the American Association for Geriatric Psychiatry.

He presented a secondary analysis of a double-blind multicenter trial in which 230 patients with a major unipolar or bipolar depressive episode and a mean baseline score of 35 on the 24-item Hamilton Rating Scale for Depression were randomized to one of the three ECT electrode placements. Remission rates and adverse cognitive effects were similar in all three groups, as previously shown in the primary analysis (Br. J. Psychiatry 2010;196:226-34).

Bruce Jancin/Frontline Medical News

The secondary analysis was aimed at learning if age had a differential effect upon the effectiveness of the three electrode placements. It did: RUL had a 70.4% remission rate in patients aged 60 and older, compared with 46% in the younger group. And bifrontal ECT had a 50% remission rate in older patients versus a 64.4% rate in those younger than age 60, reported Dr. Sanghani, a geriatric psychiatry fellow at Zucker Hillside Hospital in Glen Oaks, N.Y.

In contrast, the 75% remission rate with bitemporal ECT in the older group was not significantly different from the 58.3% rate in younger patients, he added.

Dr. Sanghani’s coinvestigator Dr. Georgios Petrides offered two possible explanations for the differential efficacy with age. One is that because the brain shrinks with advancing age, bifrontal electrode placement in the elderly might result in weak contact and loss of much of the stimulus, while ECT delivered via RUL placement captures much more of the brain.

"On the other hand, we always get a better response with ECT in the elderly than with younger people. So maybe depression in the elderly is a different animal than in younger people," suggested Dr. Petrides, a psychiatrist at Hofstra North Shore-LIJ School of Medicine, Glen Oaks.

Their study was funded by the National Institute of Mental Health. They reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

ORLANDO – Right unilateral electroconvulsive therapy at six times the seizure threshold is markedly more effective in severely depressed patients aged 60 and older than in those who are younger, according to a multicenter randomized trial.

Bitemporal and right unilateral (RUL) ECT proved similarly effective in older patients, and both were better than bifrontal ECT in the elderly.

"One implication of our study is that in an older patient who didn’t want bitemporal ECT or whose family didn’t, then I would choose right unilateral because it’s just as good," Dr. Sohag N. Sanghani said at the annual meeting of the American Association for Geriatric Psychiatry.

He presented a secondary analysis of a double-blind multicenter trial in which 230 patients with a major unipolar or bipolar depressive episode and a mean baseline score of 35 on the 24-item Hamilton Rating Scale for Depression were randomized to one of the three ECT electrode placements. Remission rates and adverse cognitive effects were similar in all three groups, as previously shown in the primary analysis (Br. J. Psychiatry 2010;196:226-34).

Bruce Jancin/Frontline Medical News

The secondary analysis was aimed at learning if age had a differential effect upon the effectiveness of the three electrode placements. It did: RUL had a 70.4% remission rate in patients aged 60 and older, compared with 46% in the younger group. And bifrontal ECT had a 50% remission rate in older patients versus a 64.4% rate in those younger than age 60, reported Dr. Sanghani, a geriatric psychiatry fellow at Zucker Hillside Hospital in Glen Oaks, N.Y.

In contrast, the 75% remission rate with bitemporal ECT in the older group was not significantly different from the 58.3% rate in younger patients, he added.

Dr. Sanghani’s coinvestigator Dr. Georgios Petrides offered two possible explanations for the differential efficacy with age. One is that because the brain shrinks with advancing age, bifrontal electrode placement in the elderly might result in weak contact and loss of much of the stimulus, while ECT delivered via RUL placement captures much more of the brain.

"On the other hand, we always get a better response with ECT in the elderly than with younger people. So maybe depression in the elderly is a different animal than in younger people," suggested Dr. Petrides, a psychiatrist at Hofstra North Shore-LIJ School of Medicine, Glen Oaks.

Their study was funded by the National Institute of Mental Health. They reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

WASHINGTON – Evolocumab, an investigational fully human monoclonal antibody, was associated with markedly greater LDL cholesterol reductions than ezetimibe in a phase III clinical trial of statin-intolerant patients.

"Robust LDL lowering and good tolerability make evolocumab a promising therapy for addressing the large unmet clinical need in high-risk hypercholesterolemic patients with statin intolerance," Dr. Erik S.G. Stroes said in presenting results of the phase III trial, known as GAUSS-2, at the annual meeting of the American College of Cardiology.

Evolocumab is an injected product that inhibits PCSK9 (proprotein convertase subtilisin/kexin type 9). Ezetimibe is the only well-tolerated and approved alternative available for LDL cholesterol lowering in patients who can’t take a statin.

Frontline Medical News

Recent real-world patient surveys suggest the rate of statin intolerance is 10%-20%, much more common than was initially apparent from the highly selective landmark statin clinical trials, observed Dr. Stroes, professor and chair of the department of vascular medicine at the Academic Medical Center, Amsterdam.

GAUSS-2 (the second study of Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects) was a 12-week, double-blind, phase III clinical trial that included 307 participants. All had a history of intolerance to at least two statins. The majority of GAUSS-2 participants had previously discontinued three or more statins, nearly always because of muscle aches and pains, and almost one-quarter had unsuccessfully tried four or more statins.

The mean baseline LDL cholesterol level was 193 mg/dL. Subjects were randomized 2:2:1:1 to one of four treatment arms: subcutaneously injected evolocumab at 140 mg, given biweekly plus an oral placebo; evolocumab 420 mg, given monthly plus placebo; or 10 mg/day of oral ezetimibe plus a placebo injection given either biweekly or monthly.

The primary endpoint was the percentage change in LDL cholesterol levels from baseline through week 12. The two evolocumab dosing regimens proved clinically equivalent, with mean LDL cholesterol reductions of 53% and 56%, in contrast to the 15% and 18% reductions in the two ezetimibe arms.

As in the other four phase III evolocumab trials presented at ACC 14, the PCSK9 inhibitor was well tolerated with 96% of patients randomized to evolocumab in GAUSS-2 completing the 12-week study. Given that 100% of GAUSS-2 participants had a history of intolerable muscle-related side effects during multiple prior rounds of statin therapy, it’s noteworthy that the incidence of myalgia in the evolocumab group was 8%, even lower than the 18% rate in the ezetimibe group, Dr. Stroes commented.

Frontline Medical News

At the same late-breaking clinical trials session at which Dr. Stroes presented GAUSS-2, Dr. Jennifer G. Robinson presented the results of LAPLACE-2, a randomized, double-blind, 12-week, phase III trial in which investigators looked at the lipid-lowering effects of evolocumab in conjunction with various doses of atorvastatin, rosuvastatin, and simvastatin. LAPLACE-2 (LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy) featured a complex study design in which roughly 1,900 patients with elevated LDL cholesterol levels were randomized to 1 of 24 treatment arms.

At week 12, the percent reduction in LDL cholesterol from baseline in the various evolocumab arms ranged from 55% to 76%. An LDL cholesterol level of less than 70 mg/dL was achieved in 86%-94% of patients on evolocumab and moderate-intensity statin therapy, such as atorvastatin at 10 mg/day and in 3%-95% of those on evolocumab and high-intensity statin therapy, such as atorvastatin at 80 mg/day or simvastatin at 40 mg/day.

At week 12, the mean LDL cholesterol level in patients on evolocumab plus high-intensity statin therapy was 35-38 mg/dL. In those on a moderate-intensity statin regimen, the mean LDL cholesterol level was 38-45 mg/dL, reported Dr. Robinson, professor of epidemiology and of medicine and director of the prevention intervention center at the University of Iowa, Iowa City.

With five evolocumab phase III clinical trials presented at ACC 14 showing a consistent pattern of large-scale LDL cholesterol lowering and a side effect profile essentially that of placebo, the crucial question now becomes whether achieving LDL cholesterol levels in the 35-45 mg/dL range will translate into a large reduction in cardiovascular events. All eyes have turned to the ongoing FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, in which 22,500 patients with clinical atherosclerotic cardiovascular disease are being randomized to evolocumab or placebo in combination with moderate- or high-intensity statin therapy with cardiovascular event rates as the key endpoints. Results are expected in 2018.

In the meantime, Dr. Robinson said, it’s possible that prior to the FOURIER results, the Food and Drug Administration will approve evolocumab with an indication for LDL cholesterol lowering. After all, ezetimibe was approved on the strength of far more modest lipid lowering, and in the absence of supporting outcome data. But if evolocumab were to receive marketing approval in advance of the event rate data, she added, the proper way for physicians to use it would be only in the patient groups with significant clinical unmet needs who were the focus of the phase III trials: those with statin intolerance (GAUSS-2), familial hypercholesterolemia and other genetic dyslipidemias (RUTHERFORD-2), or people whose cardiovascular risk status warrants high-intensity statin therapy but who can only tolerate moderate-intensity therapy (LAPLACE-2).

Dr. Stroes concurred. "We are absolutely not in competition with statins; we have to start with statins," he emphasized. "What I hope is that while we’re waiting for the outcome study, that we’ll be able to continue treating these patients in open-label extension studies, because they don’t have an alternative."

Discussant Dr. Joseph S. Alpert called the evolocumab results "very dramatic. Like everybody else, I’m waiting to see the outcome data. My prediction is that it’s going to be a positive trial," said Dr. Alpert, professor of medicine and director of the coronary care unit at University of Arizona Medical Center, Tucson.

If that proves to be the case, he added, it would probably result in a return to the ‘treat to target/know your LDL number’ approach that the ACC/American Heart Association guidelines turned away from last year in an enormously controversial move.

Simultaneous with Dr. Stroes’s presentation of GAUSS-2, the study was published online (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.019]).

Dr. Stroes and Dr. Robinson serve as consultants to Amgen, which sponsored the studies.

bjancin@frontlinemedcom.com

WASHINGTON – Evolocumab, an investigational fully human monoclonal antibody, was associated with markedly greater LDL cholesterol reductions than ezetimibe in a phase III clinical trial of statin-intolerant patients.

"Robust LDL lowering and good tolerability make evolocumab a promising therapy for addressing the large unmet clinical need in high-risk hypercholesterolemic patients with statin intolerance," Dr. Erik S.G. Stroes said in presenting results of the phase III trial, known as GAUSS-2, at the annual meeting of the American College of Cardiology.

Evolocumab is an injected product that inhibits PCSK9 (proprotein convertase subtilisin/kexin type 9). Ezetimibe is the only well-tolerated and approved alternative available for LDL cholesterol lowering in patients who can’t take a statin.

Frontline Medical News

Recent real-world patient surveys suggest the rate of statin intolerance is 10%-20%, much more common than was initially apparent from the highly selective landmark statin clinical trials, observed Dr. Stroes, professor and chair of the department of vascular medicine at the Academic Medical Center, Amsterdam.

GAUSS-2 (the second study of Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects) was a 12-week, double-blind, phase III clinical trial that included 307 participants. All had a history of intolerance to at least two statins. The majority of GAUSS-2 participants had previously discontinued three or more statins, nearly always because of muscle aches and pains, and almost one-quarter had unsuccessfully tried four or more statins.

The mean baseline LDL cholesterol level was 193 mg/dL. Subjects were randomized 2:2:1:1 to one of four treatment arms: subcutaneously injected evolocumab at 140 mg, given biweekly plus an oral placebo; evolocumab 420 mg, given monthly plus placebo; or 10 mg/day of oral ezetimibe plus a placebo injection given either biweekly or monthly.

The primary endpoint was the percentage change in LDL cholesterol levels from baseline through week 12. The two evolocumab dosing regimens proved clinically equivalent, with mean LDL cholesterol reductions of 53% and 56%, in contrast to the 15% and 18% reductions in the two ezetimibe arms.

As in the other four phase III evolocumab trials presented at ACC 14, the PCSK9 inhibitor was well tolerated with 96% of patients randomized to evolocumab in GAUSS-2 completing the 12-week study. Given that 100% of GAUSS-2 participants had a history of intolerable muscle-related side effects during multiple prior rounds of statin therapy, it’s noteworthy that the incidence of myalgia in the evolocumab group was 8%, even lower than the 18% rate in the ezetimibe group, Dr. Stroes commented.

Frontline Medical News

At the same late-breaking clinical trials session at which Dr. Stroes presented GAUSS-2, Dr. Jennifer G. Robinson presented the results of LAPLACE-2, a randomized, double-blind, 12-week, phase III trial in which investigators looked at the lipid-lowering effects of evolocumab in conjunction with various doses of atorvastatin, rosuvastatin, and simvastatin. LAPLACE-2 (LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy) featured a complex study design in which roughly 1,900 patients with elevated LDL cholesterol levels were randomized to 1 of 24 treatment arms.

At week 12, the percent reduction in LDL cholesterol from baseline in the various evolocumab arms ranged from 55% to 76%. An LDL cholesterol level of less than 70 mg/dL was achieved in 86%-94% of patients on evolocumab and moderate-intensity statin therapy, such as atorvastatin at 10 mg/day and in 3%-95% of those on evolocumab and high-intensity statin therapy, such as atorvastatin at 80 mg/day or simvastatin at 40 mg/day.

At week 12, the mean LDL cholesterol level in patients on evolocumab plus high-intensity statin therapy was 35-38 mg/dL. In those on a moderate-intensity statin regimen, the mean LDL cholesterol level was 38-45 mg/dL, reported Dr. Robinson, professor of epidemiology and of medicine and director of the prevention intervention center at the University of Iowa, Iowa City.

With five evolocumab phase III clinical trials presented at ACC 14 showing a consistent pattern of large-scale LDL cholesterol lowering and a side effect profile essentially that of placebo, the crucial question now becomes whether achieving LDL cholesterol levels in the 35-45 mg/dL range will translate into a large reduction in cardiovascular events. All eyes have turned to the ongoing FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, in which 22,500 patients with clinical atherosclerotic cardiovascular disease are being randomized to evolocumab or placebo in combination with moderate- or high-intensity statin therapy with cardiovascular event rates as the key endpoints. Results are expected in 2018.

In the meantime, Dr. Robinson said, it’s possible that prior to the FOURIER results, the Food and Drug Administration will approve evolocumab with an indication for LDL cholesterol lowering. After all, ezetimibe was approved on the strength of far more modest lipid lowering, and in the absence of supporting outcome data. But if evolocumab were to receive marketing approval in advance of the event rate data, she added, the proper way for physicians to use it would be only in the patient groups with significant clinical unmet needs who were the focus of the phase III trials: those with statin intolerance (GAUSS-2), familial hypercholesterolemia and other genetic dyslipidemias (RUTHERFORD-2), or people whose cardiovascular risk status warrants high-intensity statin therapy but who can only tolerate moderate-intensity therapy (LAPLACE-2).

Dr. Stroes concurred. "We are absolutely not in competition with statins; we have to start with statins," he emphasized. "What I hope is that while we’re waiting for the outcome study, that we’ll be able to continue treating these patients in open-label extension studies, because they don’t have an alternative."

Discussant Dr. Joseph S. Alpert called the evolocumab results "very dramatic. Like everybody else, I’m waiting to see the outcome data. My prediction is that it’s going to be a positive trial," said Dr. Alpert, professor of medicine and director of the coronary care unit at University of Arizona Medical Center, Tucson.

If that proves to be the case, he added, it would probably result in a return to the ‘treat to target/know your LDL number’ approach that the ACC/American Heart Association guidelines turned away from last year in an enormously controversial move.

Simultaneous with Dr. Stroes’s presentation of GAUSS-2, the study was published online (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.019]).

Dr. Stroes and Dr. Robinson serve as consultants to Amgen, which sponsored the studies.

bjancin@frontlinemedcom.com

WASHINGTON – Evolocumab, an investigational fully human monoclonal antibody, was associated with markedly greater LDL cholesterol reductions than ezetimibe in a phase III clinical trial of statin-intolerant patients.

"Robust LDL lowering and good tolerability make evolocumab a promising therapy for addressing the large unmet clinical need in high-risk hypercholesterolemic patients with statin intolerance," Dr. Erik S.G. Stroes said in presenting results of the phase III trial, known as GAUSS-2, at the annual meeting of the American College of Cardiology.

Evolocumab is an injected product that inhibits PCSK9 (proprotein convertase subtilisin/kexin type 9). Ezetimibe is the only well-tolerated and approved alternative available for LDL cholesterol lowering in patients who can’t take a statin.

Frontline Medical News

Recent real-world patient surveys suggest the rate of statin intolerance is 10%-20%, much more common than was initially apparent from the highly selective landmark statin clinical trials, observed Dr. Stroes, professor and chair of the department of vascular medicine at the Academic Medical Center, Amsterdam.

GAUSS-2 (the second study of Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects) was a 12-week, double-blind, phase III clinical trial that included 307 participants. All had a history of intolerance to at least two statins. The majority of GAUSS-2 participants had previously discontinued three or more statins, nearly always because of muscle aches and pains, and almost one-quarter had unsuccessfully tried four or more statins.

The mean baseline LDL cholesterol level was 193 mg/dL. Subjects were randomized 2:2:1:1 to one of four treatment arms: subcutaneously injected evolocumab at 140 mg, given biweekly plus an oral placebo; evolocumab 420 mg, given monthly plus placebo; or 10 mg/day of oral ezetimibe plus a placebo injection given either biweekly or monthly.

The primary endpoint was the percentage change in LDL cholesterol levels from baseline through week 12. The two evolocumab dosing regimens proved clinically equivalent, with mean LDL cholesterol reductions of 53% and 56%, in contrast to the 15% and 18% reductions in the two ezetimibe arms.

As in the other four phase III evolocumab trials presented at ACC 14, the PCSK9 inhibitor was well tolerated with 96% of patients randomized to evolocumab in GAUSS-2 completing the 12-week study. Given that 100% of GAUSS-2 participants had a history of intolerable muscle-related side effects during multiple prior rounds of statin therapy, it’s noteworthy that the incidence of myalgia in the evolocumab group was 8%, even lower than the 18% rate in the ezetimibe group, Dr. Stroes commented.

Frontline Medical News

At the same late-breaking clinical trials session at which Dr. Stroes presented GAUSS-2, Dr. Jennifer G. Robinson presented the results of LAPLACE-2, a randomized, double-blind, 12-week, phase III trial in which investigators looked at the lipid-lowering effects of evolocumab in conjunction with various doses of atorvastatin, rosuvastatin, and simvastatin. LAPLACE-2 (LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy) featured a complex study design in which roughly 1,900 patients with elevated LDL cholesterol levels were randomized to 1 of 24 treatment arms.

At week 12, the percent reduction in LDL cholesterol from baseline in the various evolocumab arms ranged from 55% to 76%. An LDL cholesterol level of less than 70 mg/dL was achieved in 86%-94% of patients on evolocumab and moderate-intensity statin therapy, such as atorvastatin at 10 mg/day and in 3%-95% of those on evolocumab and high-intensity statin therapy, such as atorvastatin at 80 mg/day or simvastatin at 40 mg/day.

At week 12, the mean LDL cholesterol level in patients on evolocumab plus high-intensity statin therapy was 35-38 mg/dL. In those on a moderate-intensity statin regimen, the mean LDL cholesterol level was 38-45 mg/dL, reported Dr. Robinson, professor of epidemiology and of medicine and director of the prevention intervention center at the University of Iowa, Iowa City.

With five evolocumab phase III clinical trials presented at ACC 14 showing a consistent pattern of large-scale LDL cholesterol lowering and a side effect profile essentially that of placebo, the crucial question now becomes whether achieving LDL cholesterol levels in the 35-45 mg/dL range will translate into a large reduction in cardiovascular events. All eyes have turned to the ongoing FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, in which 22,500 patients with clinical atherosclerotic cardiovascular disease are being randomized to evolocumab or placebo in combination with moderate- or high-intensity statin therapy with cardiovascular event rates as the key endpoints. Results are expected in 2018.

In the meantime, Dr. Robinson said, it’s possible that prior to the FOURIER results, the Food and Drug Administration will approve evolocumab with an indication for LDL cholesterol lowering. After all, ezetimibe was approved on the strength of far more modest lipid lowering, and in the absence of supporting outcome data. But if evolocumab were to receive marketing approval in advance of the event rate data, she added, the proper way for physicians to use it would be only in the patient groups with significant clinical unmet needs who were the focus of the phase III trials: those with statin intolerance (GAUSS-2), familial hypercholesterolemia and other genetic dyslipidemias (RUTHERFORD-2), or people whose cardiovascular risk status warrants high-intensity statin therapy but who can only tolerate moderate-intensity therapy (LAPLACE-2).

Dr. Stroes concurred. "We are absolutely not in competition with statins; we have to start with statins," he emphasized. "What I hope is that while we’re waiting for the outcome study, that we’ll be able to continue treating these patients in open-label extension studies, because they don’t have an alternative."

Discussant Dr. Joseph S. Alpert called the evolocumab results "very dramatic. Like everybody else, I’m waiting to see the outcome data. My prediction is that it’s going to be a positive trial," said Dr. Alpert, professor of medicine and director of the coronary care unit at University of Arizona Medical Center, Tucson.

If that proves to be the case, he added, it would probably result in a return to the ‘treat to target/know your LDL number’ approach that the ACC/American Heart Association guidelines turned away from last year in an enormously controversial move.

Simultaneous with Dr. Stroes’s presentation of GAUSS-2, the study was published online (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.019]).

Dr. Stroes and Dr. Robinson serve as consultants to Amgen, which sponsored the studies.

bjancin@frontlinemedcom.com

WASHINGTON – In the large STABILITY trial, darapladib did not significantly reduce the primary endpoint of cardiovascular death, MI, or stroke in patients with stable coronary disease.

The novel selective oral inhibitor of lipoprotein-associated phospholipase A has been shown to reduce the enzyme by 60%. The aim of this study was to reduce it within coronary plaque.

Despite the negative outcome, investigator Dr. Harvey D. White told us in an interview at the annual meeting of the American College of Cardiology that there is more to learn about darapladib, as a secondary endpoint of reducing cardiovascular death, MI, and urgent revascularization was nominally significant.

bjancin@frontlinemedcom.com

WASHINGTON – In the large STABILITY trial, darapladib did not significantly reduce the primary endpoint of cardiovascular death, MI, or stroke in patients with stable coronary disease.

The novel selective oral inhibitor of lipoprotein-associated phospholipase A has been shown to reduce the enzyme by 60%. The aim of this study was to reduce it within coronary plaque.

Despite the negative outcome, investigator Dr. Harvey D. White told us in an interview at the annual meeting of the American College of Cardiology that there is more to learn about darapladib, as a secondary endpoint of reducing cardiovascular death, MI, and urgent revascularization was nominally significant.

bjancin@frontlinemedcom.com

WASHINGTON – In the large STABILITY trial, darapladib did not significantly reduce the primary endpoint of cardiovascular death, MI, or stroke in patients with stable coronary disease.

The novel selective oral inhibitor of lipoprotein-associated phospholipase A has been shown to reduce the enzyme by 60%. The aim of this study was to reduce it within coronary plaque.

Despite the negative outcome, investigator Dr. Harvey D. White told us in an interview at the annual meeting of the American College of Cardiology that there is more to learn about darapladib, as a secondary endpoint of reducing cardiovascular death, MI, and urgent revascularization was nominally significant.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The topical immunomodulator imiquimod appears to be beneficial therapy in selected patients with lentigo maligna or lentigo maligna melanoma, according to the largest case series to date.

"Based upon our experience, imiquimod 5% cream is a viable option as primary or adjunctive therapy of lentigo maligna and the in situ component of lentigo maligna melanoma in patients where surgery is really not feasible, or you’ve optimized surgical margins without achieving a clear histologic margin. I emphasize this should only be considered for in situ melanoma; we’re not using it to treat invasive melanoma," Dr. Susan M. Swetter said at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

A cautionary note: Imiquimod (Aldara) for lentigo maligna (LM) is off-label therapy. It’s crucial to discuss with candidates the limitations of nonsurgical treatment for LM and lentigo maligna melanoma (LMM), which includes increased risk of local recurrence because of the lack of margin control, the possibility of a missed invasive melanoma, and the lack of supporting evidence from randomized trials with long-term follow-up.

"When we’re talking about imiquimod as potential treatment for lentigo maligna – and I can’t emphasize this enough – it requires close clinical follow-up, [carefully] documented discussion with the patient, and strong patient compliance. We have had cases of lentigo maligna melanoma where there have been metastases, not because of the in situ component, but because of the initial invasive tumor. You’ve got to follow these patients long term like a hawk. I follow them with Wood’s lamp and dermoscopy, and I biopsy any pigmentation," said Dr. Swetter, professor of dermatology and director of the pigmented lesion and cutaneous melanoma clinic at Stanford (Calif.) University Medical Center.

That being said, there are many scenarios in which surgical excision – the recommended first-line treatment for LM and LMM – might not be feasible. These include the sizable numbers of patients of advanced age who have limiting comorbid medical conditions or cognitive impairment. Also, LM has a strong predilection for the head and neck, and some affected patients avidly wish to avoid potentially disfiguring surgery.

Dr. Swetter presented a retrospective study of 60 patients with 62 LM or LMM lesions treated with imiquimod 5% cream at Stanford or the Veterans Affairs Palo Alto Health Care System. Most she treated personally. Imiquimod was primary therapy in 20 cases and adjuvant therapy following failed surgical attempts to achieve histologic clearance in the rest.

Pathologically, 45% of the lesions were LM, 29% were atypical intraepidermal melanocytic proliferations or poorly evolving LM, and 26% were LMM with histologic transection of LM and excision of the invasive melanoma component. Three-quarters of treated lesions were on the head or neck.

The lesions had a mean Breslow depth of 1.17 mm. Prior to imiquimod, half of the patients had one excision and another 19% had two or more. The mean duration of imiquimod therapy was 10.9 weeks, with a mean post treatment follow-up of 38 months.

"I typically treat to a 2-cm margin around the lesion," the dermatologist noted.

The overall clinical or histologic clearance rate was 86%. This is strikingly similar to the collective 82% rate in 46 reports involving 264 treated patients described in a published review by dermatologists at the University of Colorado, Denver (Dermatol. Surg. 2012;38:937-46).

An inflammatory response to imiquimod was predictive of favorable treatment outcome, especially in patients using the topical agent as primary therapy. Of the 20 patients who used imiquimod as primary therapy, all 16 who experienced clinical and/or histologic clearance had an initial inflammatory response. In contrast, none of the four clinical nonresponders showed an inflammatory response.

Outcomes weren’t quite as good in patients using imiquimod as adjuvant therapy.

"This is likely related to more challenging cases in the adjuvant setting, where the patients may have failed multiple attempts at wide local excision for histologic clearance," Dr. Swetter surmised.

Although the use of imiquimod as treatment for LM remains off label, it’s worth noting that it receives support in major practice guidelines. National Comprehensive Cancer Network guidelines recommend consideration of topical imiquimod or radiotherapy as adjunctive treatment for LM in selected patients after optimal surgery, with a level 2B recommendation. And the American Academy of Dermatology lists imiquimod as among the adjunctive options (J. Am. Acad. Dermatol. 2009; 61:865-7). What’s really needed now, according to Dr. Swetter, is a randomized controlled trial to firmly demonstrate benefit.

Session chair Dr. Allan C. Halpern said he and his colleagues have also been using topical imiquimod to treat LM with impressive results.

"What we’ve been doing, without literature to support it, is a broad shave biopsy, essentially removing the lesion, and then going right in with imiquimod before the patient heals. We’ve gotten some really wonderful clinical results," said Dr. Halpern, chief of the dermatology service at Memorial Sloan-Kettering Cancer Center in New York.

"That said, I think it’s important to remind people that – even with surgery – we do see occasional recurrences of desmoplastic melanomas in association with prior lentigo maligna. There’s no reason to think that’s going to be any less common in the imiquimod era. It’s going to happen to us," he cautioned.

Dr. Swetter reported having no financial conflicts. Dr. Halpern has received research grants from SciBase, DermTech, Caliber, and Canfield.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The topical immunomodulator imiquimod appears to be beneficial therapy in selected patients with lentigo maligna or lentigo maligna melanoma, according to the largest case series to date.

"Based upon our experience, imiquimod 5% cream is a viable option as primary or adjunctive therapy of lentigo maligna and the in situ component of lentigo maligna melanoma in patients where surgery is really not feasible, or you’ve optimized surgical margins without achieving a clear histologic margin. I emphasize this should only be considered for in situ melanoma; we’re not using it to treat invasive melanoma," Dr. Susan M. Swetter said at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

A cautionary note: Imiquimod (Aldara) for lentigo maligna (LM) is off-label therapy. It’s crucial to discuss with candidates the limitations of nonsurgical treatment for LM and lentigo maligna melanoma (LMM), which includes increased risk of local recurrence because of the lack of margin control, the possibility of a missed invasive melanoma, and the lack of supporting evidence from randomized trials with long-term follow-up.

"When we’re talking about imiquimod as potential treatment for lentigo maligna – and I can’t emphasize this enough – it requires close clinical follow-up, [carefully] documented discussion with the patient, and strong patient compliance. We have had cases of lentigo maligna melanoma where there have been metastases, not because of the in situ component, but because of the initial invasive tumor. You’ve got to follow these patients long term like a hawk. I follow them with Wood’s lamp and dermoscopy, and I biopsy any pigmentation," said Dr. Swetter, professor of dermatology and director of the pigmented lesion and cutaneous melanoma clinic at Stanford (Calif.) University Medical Center.

That being said, there are many scenarios in which surgical excision – the recommended first-line treatment for LM and LMM – might not be feasible. These include the sizable numbers of patients of advanced age who have limiting comorbid medical conditions or cognitive impairment. Also, LM has a strong predilection for the head and neck, and some affected patients avidly wish to avoid potentially disfiguring surgery.

Dr. Swetter presented a retrospective study of 60 patients with 62 LM or LMM lesions treated with imiquimod 5% cream at Stanford or the Veterans Affairs Palo Alto Health Care System. Most she treated personally. Imiquimod was primary therapy in 20 cases and adjuvant therapy following failed surgical attempts to achieve histologic clearance in the rest.

Pathologically, 45% of the lesions were LM, 29% were atypical intraepidermal melanocytic proliferations or poorly evolving LM, and 26% were LMM with histologic transection of LM and excision of the invasive melanoma component. Three-quarters of treated lesions were on the head or neck.

The lesions had a mean Breslow depth of 1.17 mm. Prior to imiquimod, half of the patients had one excision and another 19% had two or more. The mean duration of imiquimod therapy was 10.9 weeks, with a mean post treatment follow-up of 38 months.

"I typically treat to a 2-cm margin around the lesion," the dermatologist noted.

The overall clinical or histologic clearance rate was 86%. This is strikingly similar to the collective 82% rate in 46 reports involving 264 treated patients described in a published review by dermatologists at the University of Colorado, Denver (Dermatol. Surg. 2012;38:937-46).

An inflammatory response to imiquimod was predictive of favorable treatment outcome, especially in patients using the topical agent as primary therapy. Of the 20 patients who used imiquimod as primary therapy, all 16 who experienced clinical and/or histologic clearance had an initial inflammatory response. In contrast, none of the four clinical nonresponders showed an inflammatory response.

Outcomes weren’t quite as good in patients using imiquimod as adjuvant therapy.

"This is likely related to more challenging cases in the adjuvant setting, where the patients may have failed multiple attempts at wide local excision for histologic clearance," Dr. Swetter surmised.

Although the use of imiquimod as treatment for LM remains off label, it’s worth noting that it receives support in major practice guidelines. National Comprehensive Cancer Network guidelines recommend consideration of topical imiquimod or radiotherapy as adjunctive treatment for LM in selected patients after optimal surgery, with a level 2B recommendation. And the American Academy of Dermatology lists imiquimod as among the adjunctive options (J. Am. Acad. Dermatol. 2009; 61:865-7). What’s really needed now, according to Dr. Swetter, is a randomized controlled trial to firmly demonstrate benefit.

Session chair Dr. Allan C. Halpern said he and his colleagues have also been using topical imiquimod to treat LM with impressive results.

"What we’ve been doing, without literature to support it, is a broad shave biopsy, essentially removing the lesion, and then going right in with imiquimod before the patient heals. We’ve gotten some really wonderful clinical results," said Dr. Halpern, chief of the dermatology service at Memorial Sloan-Kettering Cancer Center in New York.

"That said, I think it’s important to remind people that – even with surgery – we do see occasional recurrences of desmoplastic melanomas in association with prior lentigo maligna. There’s no reason to think that’s going to be any less common in the imiquimod era. It’s going to happen to us," he cautioned.

Dr. Swetter reported having no financial conflicts. Dr. Halpern has received research grants from SciBase, DermTech, Caliber, and Canfield.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The topical immunomodulator imiquimod appears to be beneficial therapy in selected patients with lentigo maligna or lentigo maligna melanoma, according to the largest case series to date.

"Based upon our experience, imiquimod 5% cream is a viable option as primary or adjunctive therapy of lentigo maligna and the in situ component of lentigo maligna melanoma in patients where surgery is really not feasible, or you’ve optimized surgical margins without achieving a clear histologic margin. I emphasize this should only be considered for in situ melanoma; we’re not using it to treat invasive melanoma," Dr. Susan M. Swetter said at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

A cautionary note: Imiquimod (Aldara) for lentigo maligna (LM) is off-label therapy. It’s crucial to discuss with candidates the limitations of nonsurgical treatment for LM and lentigo maligna melanoma (LMM), which includes increased risk of local recurrence because of the lack of margin control, the possibility of a missed invasive melanoma, and the lack of supporting evidence from randomized trials with long-term follow-up.

"When we’re talking about imiquimod as potential treatment for lentigo maligna – and I can’t emphasize this enough – it requires close clinical follow-up, [carefully] documented discussion with the patient, and strong patient compliance. We have had cases of lentigo maligna melanoma where there have been metastases, not because of the in situ component, but because of the initial invasive tumor. You’ve got to follow these patients long term like a hawk. I follow them with Wood’s lamp and dermoscopy, and I biopsy any pigmentation," said Dr. Swetter, professor of dermatology and director of the pigmented lesion and cutaneous melanoma clinic at Stanford (Calif.) University Medical Center.

That being said, there are many scenarios in which surgical excision – the recommended first-line treatment for LM and LMM – might not be feasible. These include the sizable numbers of patients of advanced age who have limiting comorbid medical conditions or cognitive impairment. Also, LM has a strong predilection for the head and neck, and some affected patients avidly wish to avoid potentially disfiguring surgery.

Dr. Swetter presented a retrospective study of 60 patients with 62 LM or LMM lesions treated with imiquimod 5% cream at Stanford or the Veterans Affairs Palo Alto Health Care System. Most she treated personally. Imiquimod was primary therapy in 20 cases and adjuvant therapy following failed surgical attempts to achieve histologic clearance in the rest.

Pathologically, 45% of the lesions were LM, 29% were atypical intraepidermal melanocytic proliferations or poorly evolving LM, and 26% were LMM with histologic transection of LM and excision of the invasive melanoma component. Three-quarters of treated lesions were on the head or neck.

The lesions had a mean Breslow depth of 1.17 mm. Prior to imiquimod, half of the patients had one excision and another 19% had two or more. The mean duration of imiquimod therapy was 10.9 weeks, with a mean post treatment follow-up of 38 months.

"I typically treat to a 2-cm margin around the lesion," the dermatologist noted.

The overall clinical or histologic clearance rate was 86%. This is strikingly similar to the collective 82% rate in 46 reports involving 264 treated patients described in a published review by dermatologists at the University of Colorado, Denver (Dermatol. Surg. 2012;38:937-46).

An inflammatory response to imiquimod was predictive of favorable treatment outcome, especially in patients using the topical agent as primary therapy. Of the 20 patients who used imiquimod as primary therapy, all 16 who experienced clinical and/or histologic clearance had an initial inflammatory response. In contrast, none of the four clinical nonresponders showed an inflammatory response.

Outcomes weren’t quite as good in patients using imiquimod as adjuvant therapy.

"This is likely related to more challenging cases in the adjuvant setting, where the patients may have failed multiple attempts at wide local excision for histologic clearance," Dr. Swetter surmised.

Although the use of imiquimod as treatment for LM remains off label, it’s worth noting that it receives support in major practice guidelines. National Comprehensive Cancer Network guidelines recommend consideration of topical imiquimod or radiotherapy as adjunctive treatment for LM in selected patients after optimal surgery, with a level 2B recommendation. And the American Academy of Dermatology lists imiquimod as among the adjunctive options (J. Am. Acad. Dermatol. 2009; 61:865-7). What’s really needed now, according to Dr. Swetter, is a randomized controlled trial to firmly demonstrate benefit.

Session chair Dr. Allan C. Halpern said he and his colleagues have also been using topical imiquimod to treat LM with impressive results.

"What we’ve been doing, without literature to support it, is a broad shave biopsy, essentially removing the lesion, and then going right in with imiquimod before the patient heals. We’ve gotten some really wonderful clinical results," said Dr. Halpern, chief of the dermatology service at Memorial Sloan-Kettering Cancer Center in New York.

"That said, I think it’s important to remind people that – even with surgery – we do see occasional recurrences of desmoplastic melanomas in association with prior lentigo maligna. There’s no reason to think that’s going to be any less common in the imiquimod era. It’s going to happen to us," he cautioned.

Dr. Swetter reported having no financial conflicts. Dr. Halpern has received research grants from SciBase, DermTech, Caliber, and Canfield.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WASHINGTON – The novel low-density lipoprotein cholesterol–lowering agent evolocumab took day 1 of the annual meeting of the American College of Cardiology by storm on the strength of three resoundingly positive phase III clinical trials.

"These three studies presented today I think are nothing short of revolutionary," session cochair Dr. Gregory S. Thomas said in an interview after the presentations.

"To be able to uniformly achieve a 50%-60% further reduction in LDL in patients already on diet, on statins, and often on ezetimibe, and to bring almost all the patients down to LDL levels that most clinicians would be satisfied with is just remarkable," observed Dr. Thomas, medical director of the MemorialCare Heart & Vascular Institute at Long Beach (Calif.) Memorial.

Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that plays a major role in regulating LDL cholesterol levels. In earlier phase II studies it showed impressive efficacy in LDL lowering. As a result, the eagerly anticipated phase III trials drew throngs. Even before the new-research session got underway, fire marshals stood in the doorways and turned away large numbers of disappointed meeting attendees.

The showstopper was DESCARTES (Durable Effect of PCSK9 Antibody Compared with Placebo Study), to date by far the longest randomized, double-blind, placebo-controlled clinical trial of any PCSK9 inhibitor. The 52-week study randomized 901 participants 2:1 to evolocumab by subcutaneous injection at 420 mg every 4 weeks or placebo on top of background lipid-lowering therapy optimized in an effort to reach National Cholesterol Education Campaign ATP III LDL goals. The background therapy options ranged from diet alone, to diet plus atorvastatin at either 10 or 80 mg/day, to high-dose atorvastatin plus ezetimibe at 10 mg/day. DESCARTES participants had to have an LDL cholesterol level of 75 mg/dL or more after up to 16 weeks of the run-in background therapy. At randomization, their mean LDL cholesterol level was 104 mg/dL.

The mean placebo-adjusted reduction in LDL cholesterol from baseline to week 52 – the primary study endpoint – was 57% in the evolocumab group. Moreover, 82% of patients in the evolocumab group achieved an LDL below 70 mg/dL, compared with just 6.4% of the control group, reported Dr. Dirk J. Blom of the University of Cape Town, South Africa.

The LDL cholesterol lowering was accompanied by a placebo-adjusted 42% reduction in apolipoprotein B, a 28% drop in lipoprotein(a), a 9% decrease in triglycerides, a 6% boost in HDL cholesterol, and a modest but statistically significant 2% rise in apolipoprotein A1, he added.

There was no diminution in evolocumab’s LDL cholesterol–lowering effect over the duration of the study. It was the same at week 52 as at week 12. The evolocumab group showed no significant changes over time in fasting blood glucose or glycosylated hemoglobin. Rates and types of all adverse events, including injection site reactions, abnormal liver function tests, and elevations in creatine kinase, were essentially the same in the evolocumab and control groups. One patient developed transient anti-evolocumab–binding antibodies during treatment with the PCSK9 inhibitor; however, no one developed anti-evolocumab–neutralizing antibodies.

The same themes of massive reductions in LDL cholesterol along with a side effect profile mirroring placebo emerged from the other two phase III trials, RUTHERFORD-2 and MENDEL-2.

RUTHERFORD-2 (Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder) was a 12-week, double-blind, placebo-controlled trial in 329 patients with heterozygous familial hypercholesterolemia. Their mean baseline LDL cholesterol was 154 mg/dL, even though all were on statin therapy and about 60% were also on ezetimibe. They were randomized 2:1 to evolocumab or placebo on top of their background lipid-lowering regimen. The evolocumab group was randomized to monthly injections at 420 mg, as in DESCARTES, or to home biweekly injections at 140 mg delivered by prefilled autoinjector using a 27-gauge needle. The two dosing regimens proved clinically equivalent in efficacy and lack of side effects. At 12 weeks, 68% of patients on biweekly evolocumab and 63% on monthly therapy had an LDL cholesterol level below 70 mg/dL, compared with 2% on placebo, according to Dr. Frederick J. Raal of the University of the Witwatersrand in Johannesburg, South Africa.

A new and effective treatment option for patients with heterozygous familial hypercholesterolemia would be most welcome, he noted. This is the most common of all autosomal dominant inherited disorders, with an estimated prevalence of 1 in roughly 300, meaning more than 1 million people are affected in the United States alone. The disorder is characterized by markedly elevated LDL levels that often can’t be brought down to target despite maximal current therapies. Untreated men with heterozygous familial hypercholesterolemia typically have their first coronary event in their 40s, women a decade later.

Dr. Michael J. Koren presented the findings of MENDEL-2. This 12-week, double-blind, placebo- and ezetimibe-controlled, multicenter, phase-III study included 614 patients with a baseline LDL cholesterol level of 100-190 mg/dL. None were permitted to be on a statin. Statins are known to upregulate PCSK9 production, so it was important to find out whether evolocumab performs differently depending upon whether patients are on that workhorse therapy. As in RUTHERFORD-2, the evolocumab group was randomized to 140 mg biweekly by autoinjector or to monthly treatment at 420 mg. Over the course of 12 weeks, LDL dropped by 57% with biweekly evolocumab and 56% with monthly injections.

"Though we anticipate that evolocumab will find use primarily as a treatment for high-risk patients in conjunction with statins, MENDEL-2 has demonstrated that evolocumab produces large LDL-lowering effects as monotherapy," said Dr. Koren of the Jacksonville (Fla.) Center for Clinical Research.

Dr. Thomas, the session cochair, said it will be interesting to see how the Food and Drug Administration responds to the new phase III data. Large studies with cardiovascular event endpoints are ongoing. The FDA may want to wait for evidence from those studies showing that large-magnitude LDL cholesterol lowering reduces events, or the agency might be inclined to approve PCSK9 inhibitor therapy for selected high-risk populations.

"I think the RUTHERFORD-2 trial in heterozygous familial hypercholesterolemia patients was particularly interesting. Perhaps the new agents could first be approved for use in that population, because those patients clearly have a very high rate of premature coronary disease," the cardiologist said.

As for safety, Dr. Thomas said "We’ve continued to look for problems with these agents, but so far, we can’t find any off-target effects. Results 2-3 years out in ongoing open-label studies will be very important."

Dr. Blom, Dr. Raal, and Dr. Koren reported receiving research grants and consultant’s fees from Amgen, which sponsored the evolocumab phase III trials. Dr. Thomas reported receiving research grants and consultant’s fees from Sanofi, which is developing another PCSK9 inhibitor.

Simultaneous with Dr. Blom’s presentation, the DESCARTES results were published online (N. Engl. J. Med. 2014 March 29 [doi:10.1056/NEJMoa1316222]). The MENDEL-2 study was also simultaneously published (J. Am. Coll. Cardiol. 2014 March 29 [doi:10.1016/j.jacc.2014.03.018]).

bjancin@frontlinemedcom.com

WASHINGTON – The novel low-density lipoprotein cholesterol–lowering agent evolocumab took day 1 of the annual meeting of the American College of Cardiology by storm on the strength of three resoundingly positive phase III clinical trials.

"These three studies presented today I think are nothing short of revolutionary," session cochair Dr. Gregory S. Thomas said in an interview after the presentations.

"To be able to uniformly achieve a 50%-60% further reduction in LDL in patients already on diet, on statins, and often on ezetimibe, and to bring almost all the patients down to LDL levels that most clinicians would be satisfied with is just remarkable," observed Dr. Thomas, medical director of the MemorialCare Heart & Vascular Institute at Long Beach (Calif.) Memorial.

Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that plays a major role in regulating LDL cholesterol levels. In earlier phase II studies it showed impressive efficacy in LDL lowering. As a result, the eagerly anticipated phase III trials drew throngs. Even before the new-research session got underway, fire marshals stood in the doorways and turned away large numbers of disappointed meeting attendees.

The showstopper was DESCARTES (Durable Effect of PCSK9 Antibody Compared with Placebo Study), to date by far the longest randomized, double-blind, placebo-controlled clinical trial of any PCSK9 inhibitor. The 52-week study randomized 901 participants 2:1 to evolocumab by subcutaneous injection at 420 mg every 4 weeks or placebo on top of background lipid-lowering therapy optimized in an effort to reach National Cholesterol Education Campaign ATP III LDL goals. The background therapy options ranged from diet alone, to diet plus atorvastatin at either 10 or 80 mg/day, to high-dose atorvastatin plus ezetimibe at 10 mg/day. DESCARTES participants had to have an LDL cholesterol level of 75 mg/dL or more after up to 16 weeks of the run-in background therapy. At randomization, their mean LDL cholesterol level was 104 mg/dL.

The mean placebo-adjusted reduction in LDL cholesterol from baseline to week 52 – the primary study endpoint – was 57% in the evolocumab group. Moreover, 82% of patients in the evolocumab group achieved an LDL below 70 mg/dL, compared with just 6.4% of the control group, reported Dr. Dirk J. Blom of the University of Cape Town, South Africa.

The LDL cholesterol lowering was accompanied by a placebo-adjusted 42% reduction in apolipoprotein B, a 28% drop in lipoprotein(a), a 9% decrease in triglycerides, a 6% boost in HDL cholesterol, and a modest but statistically significant 2% rise in apolipoprotein A1, he added.

There was no diminution in evolocumab’s LDL cholesterol–lowering effect over the duration of the study. It was the same at week 52 as at week 12. The evolocumab group showed no significant changes over time in fasting blood glucose or glycosylated hemoglobin. Rates and types of all adverse events, including injection site reactions, abnormal liver function tests, and elevations in creatine kinase, were essentially the same in the evolocumab and control groups. One patient developed transient anti-evolocumab–binding antibodies during treatment with the PCSK9 inhibitor; however, no one developed anti-evolocumab–neutralizing antibodies.

The same themes of massive reductions in LDL cholesterol along with a side effect profile mirroring placebo emerged from the other two phase III trials, RUTHERFORD-2 and MENDEL-2.

RUTHERFORD-2 (Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder) was a 12-week, double-blind, placebo-controlled trial in 329 patients with heterozygous familial hypercholesterolemia. Their mean baseline LDL cholesterol was 154 mg/dL, even though all were on statin therapy and about 60% were also on ezetimibe. They were randomized 2:1 to evolocumab or placebo on top of their background lipid-lowering regimen. The evolocumab group was randomized to monthly injections at 420 mg, as in DESCARTES, or to home biweekly injections at 140 mg delivered by prefilled autoinjector using a 27-gauge needle. The two dosing regimens proved clinically equivalent in efficacy and lack of side effects. At 12 weeks, 68% of patients on biweekly evolocumab and 63% on monthly therapy had an LDL cholesterol level below 70 mg/dL, compared with 2% on placebo, according to Dr. Frederick J. Raal of the University of the Witwatersrand in Johannesburg, South Africa.

A new and effective treatment option for patients with heterozygous familial hypercholesterolemia would be most welcome, he noted. This is the most common of all autosomal dominant inherited disorders, with an estimated prevalence of 1 in roughly 300, meaning more than 1 million people are affected in the United States alone. The disorder is characterized by markedly elevated LDL levels that often can’t be brought down to target despite maximal current therapies. Untreated men with heterozygous familial hypercholesterolemia typically have their first coronary event in their 40s, women a decade later.

Dr. Michael J. Koren presented the findings of MENDEL-2. This 12-week, double-blind, placebo- and ezetimibe-controlled, multicenter, phase-III study included 614 patients with a baseline LDL cholesterol level of 100-190 mg/dL. None were permitted to be on a statin. Statins are known to upregulate PCSK9 production, so it was important to find out whether evolocumab performs differently depending upon whether patients are on that workhorse therapy. As in RUTHERFORD-2, the evolocumab group was randomized to 140 mg biweekly by autoinjector or to monthly treatment at 420 mg. Over the course of 12 weeks, LDL dropped by 57% with biweekly evolocumab and 56% with monthly injections.

"Though we anticipate that evolocumab will find use primarily as a treatment for high-risk patients in conjunction with statins, MENDEL-2 has demonstrated that evolocumab produces large LDL-lowering effects as monotherapy," said Dr. Koren of the Jacksonville (Fla.) Center for Clinical Research.

Dr. Thomas, the session cochair, said it will be interesting to see how the Food and Drug Administration responds to the new phase III data. Large studies with cardiovascular event endpoints are ongoing. The FDA may want to wait for evidence from those studies showing that large-magnitude LDL cholesterol lowering reduces events, or the agency might be inclined to approve PCSK9 inhibitor therapy for selected high-risk populations.

"I think the RUTHERFORD-2 trial in heterozygous familial hypercholesterolemia patients was particularly interesting. Perhaps the new agents could first be approved for use in that population, because those patients clearly have a very high rate of premature coronary disease," the cardiologist said.

As for safety, Dr. Thomas said "We’ve continued to look for problems with these agents, but so far, we can’t find any off-target effects. Results 2-3 years out in ongoing open-label studies will be very important."

Dr. Blom, Dr. Raal, and Dr. Koren reported receiving research grants and consultant’s fees from Amgen, which sponsored the evolocumab phase III trials. Dr. Thomas reported receiving research grants and consultant’s fees from Sanofi, which is developing another PCSK9 inhibitor.

Simultaneous with Dr. Blom’s presentation, the DESCARTES results were published online (N. Engl. J. Med. 2014 March 29 [doi:10.1056/NEJMoa1316222]). The MENDEL-2 study was also simultaneously published (J. Am. Coll. Cardiol. 2014 March 29 [doi:10.1016/j.jacc.2014.03.018]).

bjancin@frontlinemedcom.com

WASHINGTON – The novel low-density lipoprotein cholesterol–lowering agent evolocumab took day 1 of the annual meeting of the American College of Cardiology by storm on the strength of three resoundingly positive phase III clinical trials.

"These three studies presented today I think are nothing short of revolutionary," session cochair Dr. Gregory S. Thomas said in an interview after the presentations.

"To be able to uniformly achieve a 50%-60% further reduction in LDL in patients already on diet, on statins, and often on ezetimibe, and to bring almost all the patients down to LDL levels that most clinicians would be satisfied with is just remarkable," observed Dr. Thomas, medical director of the MemorialCare Heart & Vascular Institute at Long Beach (Calif.) Memorial.

Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that plays a major role in regulating LDL cholesterol levels. In earlier phase II studies it showed impressive efficacy in LDL lowering. As a result, the eagerly anticipated phase III trials drew throngs. Even before the new-research session got underway, fire marshals stood in the doorways and turned away large numbers of disappointed meeting attendees.

The showstopper was DESCARTES (Durable Effect of PCSK9 Antibody Compared with Placebo Study), to date by far the longest randomized, double-blind, placebo-controlled clinical trial of any PCSK9 inhibitor. The 52-week study randomized 901 participants 2:1 to evolocumab by subcutaneous injection at 420 mg every 4 weeks or placebo on top of background lipid-lowering therapy optimized in an effort to reach National Cholesterol Education Campaign ATP III LDL goals. The background therapy options ranged from diet alone, to diet plus atorvastatin at either 10 or 80 mg/day, to high-dose atorvastatin plus ezetimibe at 10 mg/day. DESCARTES participants had to have an LDL cholesterol level of 75 mg/dL or more after up to 16 weeks of the run-in background therapy. At randomization, their mean LDL cholesterol level was 104 mg/dL.

The mean placebo-adjusted reduction in LDL cholesterol from baseline to week 52 – the primary study endpoint – was 57% in the evolocumab group. Moreover, 82% of patients in the evolocumab group achieved an LDL below 70 mg/dL, compared with just 6.4% of the control group, reported Dr. Dirk J. Blom of the University of Cape Town, South Africa.

The LDL cholesterol lowering was accompanied by a placebo-adjusted 42% reduction in apolipoprotein B, a 28% drop in lipoprotein(a), a 9% decrease in triglycerides, a 6% boost in HDL cholesterol, and a modest but statistically significant 2% rise in apolipoprotein A1, he added.

There was no diminution in evolocumab’s LDL cholesterol–lowering effect over the duration of the study. It was the same at week 52 as at week 12. The evolocumab group showed no significant changes over time in fasting blood glucose or glycosylated hemoglobin. Rates and types of all adverse events, including injection site reactions, abnormal liver function tests, and elevations in creatine kinase, were essentially the same in the evolocumab and control groups. One patient developed transient anti-evolocumab–binding antibodies during treatment with the PCSK9 inhibitor; however, no one developed anti-evolocumab–neutralizing antibodies.

The same themes of massive reductions in LDL cholesterol along with a side effect profile mirroring placebo emerged from the other two phase III trials, RUTHERFORD-2 and MENDEL-2.

RUTHERFORD-2 (Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder) was a 12-week, double-blind, placebo-controlled trial in 329 patients with heterozygous familial hypercholesterolemia. Their mean baseline LDL cholesterol was 154 mg/dL, even though all were on statin therapy and about 60% were also on ezetimibe. They were randomized 2:1 to evolocumab or placebo on top of their background lipid-lowering regimen. The evolocumab group was randomized to monthly injections at 420 mg, as in DESCARTES, or to home biweekly injections at 140 mg delivered by prefilled autoinjector using a 27-gauge needle. The two dosing regimens proved clinically equivalent in efficacy and lack of side effects. At 12 weeks, 68% of patients on biweekly evolocumab and 63% on monthly therapy had an LDL cholesterol level below 70 mg/dL, compared with 2% on placebo, according to Dr. Frederick J. Raal of the University of the Witwatersrand in Johannesburg, South Africa.

A new and effective treatment option for patients with heterozygous familial hypercholesterolemia would be most welcome, he noted. This is the most common of all autosomal dominant inherited disorders, with an estimated prevalence of 1 in roughly 300, meaning more than 1 million people are affected in the United States alone. The disorder is characterized by markedly elevated LDL levels that often can’t be brought down to target despite maximal current therapies. Untreated men with heterozygous familial hypercholesterolemia typically have their first coronary event in their 40s, women a decade later.

Dr. Michael J. Koren presented the findings of MENDEL-2. This 12-week, double-blind, placebo- and ezetimibe-controlled, multicenter, phase-III study included 614 patients with a baseline LDL cholesterol level of 100-190 mg/dL. None were permitted to be on a statin. Statins are known to upregulate PCSK9 production, so it was important to find out whether evolocumab performs differently depending upon whether patients are on that workhorse therapy. As in RUTHERFORD-2, the evolocumab group was randomized to 140 mg biweekly by autoinjector or to monthly treatment at 420 mg. Over the course of 12 weeks, LDL dropped by 57% with biweekly evolocumab and 56% with monthly injections.

"Though we anticipate that evolocumab will find use primarily as a treatment for high-risk patients in conjunction with statins, MENDEL-2 has demonstrated that evolocumab produces large LDL-lowering effects as monotherapy," said Dr. Koren of the Jacksonville (Fla.) Center for Clinical Research.

Dr. Thomas, the session cochair, said it will be interesting to see how the Food and Drug Administration responds to the new phase III data. Large studies with cardiovascular event endpoints are ongoing. The FDA may want to wait for evidence from those studies showing that large-magnitude LDL cholesterol lowering reduces events, or the agency might be inclined to approve PCSK9 inhibitor therapy for selected high-risk populations.

"I think the RUTHERFORD-2 trial in heterozygous familial hypercholesterolemia patients was particularly interesting. Perhaps the new agents could first be approved for use in that population, because those patients clearly have a very high rate of premature coronary disease," the cardiologist said.

As for safety, Dr. Thomas said "We’ve continued to look for problems with these agents, but so far, we can’t find any off-target effects. Results 2-3 years out in ongoing open-label studies will be very important."

Dr. Blom, Dr. Raal, and Dr. Koren reported receiving research grants and consultant’s fees from Amgen, which sponsored the evolocumab phase III trials. Dr. Thomas reported receiving research grants and consultant’s fees from Sanofi, which is developing another PCSK9 inhibitor.

Simultaneous with Dr. Blom’s presentation, the DESCARTES results were published online (N. Engl. J. Med. 2014 March 29 [doi:10.1056/NEJMoa1316222]). The MENDEL-2 study was also simultaneously published (J. Am. Coll. Cardiol. 2014 March 29 [doi:10.1016/j.jacc.2014.03.018]).

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Rosacea is generally thought of as a common adult disorder with onset typically at age 30-50 years. But recent evidence indicates it can occur during early childhood, too.

Idiopathic facial aseptic granuloma – an uncommon condition sometimes mistaken for unusually early acne – is actually often an expression of childhood rosacea.

"If you see these atypical skin lesions that look like acne cysts in young children who also have facial flushing, erythema, and perhaps pustules without comedones, be sure to look carefully at the eyes. Many times, they will have ocular rosacea with recurrent chalazions, conjunctival hyperemia, or keratitis. And if you think it’s ocular rosacea, you may want to make a referral to ophthalmology for assistance with ocular rosacea management," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"I find that many times oral antibiotics are highly useful in this subset," added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and professor of clinical pediatrics and medicine at the University of California, San Diego.

The pathogenesis of idiopathic facial aseptic granuloma (IFAG) is poorly understood. French dermatologists were first to identify the link between IFAG and rosacea. In a multicenter study involving 20 girls and 18 boys with IFAG, the investigators determined that 16 of the children, or 42%, met two or more criteria for rosacea (Pediatr. Dermatol. 2013;30:429-32).

Median age at diagnosis of IFAG was 43 months, and the children were subsequently followed for a median of 3.9 years before their evaluation for possible rosacea. Eleven of the 32 (34%) children with a single IFAG lesion met criteria for childhood rosacea, as did 5 of the 6 (83%) children with multiple skin lesions.

"So be aware: Although rosacea is very uncommon in our preteens and teens, it can occur," Dr. Eichenfield observed.

He reported having served as a clinical investigator and/or consultant to Allergan, Galderma, GSK-Stiefel, and Medicis/Valeant.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Rosacea is generally thought of as a common adult disorder with onset typically at age 30-50 years. But recent evidence indicates it can occur during early childhood, too.

Idiopathic facial aseptic granuloma – an uncommon condition sometimes mistaken for unusually early acne – is actually often an expression of childhood rosacea.

"If you see these atypical skin lesions that look like acne cysts in young children who also have facial flushing, erythema, and perhaps pustules without comedones, be sure to look carefully at the eyes. Many times, they will have ocular rosacea with recurrent chalazions, conjunctival hyperemia, or keratitis. And if you think it’s ocular rosacea, you may want to make a referral to ophthalmology for assistance with ocular rosacea management," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"I find that many times oral antibiotics are highly useful in this subset," added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and professor of clinical pediatrics and medicine at the University of California, San Diego.

The pathogenesis of idiopathic facial aseptic granuloma (IFAG) is poorly understood. French dermatologists were first to identify the link between IFAG and rosacea. In a multicenter study involving 20 girls and 18 boys with IFAG, the investigators determined that 16 of the children, or 42%, met two or more criteria for rosacea (Pediatr. Dermatol. 2013;30:429-32).

Median age at diagnosis of IFAG was 43 months, and the children were subsequently followed for a median of 3.9 years before their evaluation for possible rosacea. Eleven of the 32 (34%) children with a single IFAG lesion met criteria for childhood rosacea, as did 5 of the 6 (83%) children with multiple skin lesions.

"So be aware: Although rosacea is very uncommon in our preteens and teens, it can occur," Dr. Eichenfield observed.

He reported having served as a clinical investigator and/or consultant to Allergan, Galderma, GSK-Stiefel, and Medicis/Valeant.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Rosacea is generally thought of as a common adult disorder with onset typically at age 30-50 years. But recent evidence indicates it can occur during early childhood, too.

Idiopathic facial aseptic granuloma – an uncommon condition sometimes mistaken for unusually early acne – is actually often an expression of childhood rosacea.

"If you see these atypical skin lesions that look like acne cysts in young children who also have facial flushing, erythema, and perhaps pustules without comedones, be sure to look carefully at the eyes. Many times, they will have ocular rosacea with recurrent chalazions, conjunctival hyperemia, or keratitis. And if you think it’s ocular rosacea, you may want to make a referral to ophthalmology for assistance with ocular rosacea management," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"I find that many times oral antibiotics are highly useful in this subset," added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and professor of clinical pediatrics and medicine at the University of California, San Diego.

The pathogenesis of idiopathic facial aseptic granuloma (IFAG) is poorly understood. French dermatologists were first to identify the link between IFAG and rosacea. In a multicenter study involving 20 girls and 18 boys with IFAG, the investigators determined that 16 of the children, or 42%, met two or more criteria for rosacea (Pediatr. Dermatol. 2013;30:429-32).

Median age at diagnosis of IFAG was 43 months, and the children were subsequently followed for a median of 3.9 years before their evaluation for possible rosacea. Eleven of the 32 (34%) children with a single IFAG lesion met criteria for childhood rosacea, as did 5 of the 6 (83%) children with multiple skin lesions.

"So be aware: Although rosacea is very uncommon in our preteens and teens, it can occur," Dr. Eichenfield observed.

He reported having served as a clinical investigator and/or consultant to Allergan, Galderma, GSK-Stiefel, and Medicis/Valeant.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Rosacea is generally thought of as a common adult disorder with onset typically at age 30-50 years. But recent evidence indicates it can occur during early childhood, too.

Idiopathic facial aseptic granuloma – an uncommon condition sometimes mistaken for unusually early acne – is actually often an expression of childhood rosacea.

"If you see these atypical skin lesions that look like acne cysts in young children who also have facial flushing, erythema, and perhaps pustules without comedones, be sure to look carefully at the eyes. Many times, they will have ocular rosacea with recurrent chalazions, conjunctival hyperemia, or keratitis. And if you think it’s ocular rosacea, you may want to make a referral to ophthalmology for assistance with ocular rosacea management," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"I find that many times oral antibiotics are highly useful in this subset," added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and professor of clinical pediatrics and medicine at the University of California, San Diego.

The pathogenesis of idiopathic facial aseptic granuloma (IFAG) is poorly understood. French dermatologists were first to identify the link between IFAG and rosacea. In a multicenter study involving 20 girls and 18 boys with IFAG, the investigators determined that 16 of the children, or 42%, met two or more criteria for rosacea (Pediatr. Dermatol. 2013;30:429-32).

Median age at diagnosis of IFAG was 43 months, and the children were subsequently followed for a median of 3.9 years before their evaluation for possible rosacea. Eleven of the 32 (34%) children with a single IFAG lesion met criteria for childhood rosacea, as did 5 of the 6 (83%) children with multiple skin lesions.

"So be aware: Although rosacea is very uncommon in our preteens and teens, it can occur," Dr. Eichenfield observed.

He reported having served as a clinical investigator and/or consultant to Allergan, Galderma, GSK-Stiefel, and Medicis/Valeant.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Rosacea is generally thought of as a common adult disorder with onset typically at age 30-50 years. But recent evidence indicates it can occur during early childhood, too.

Idiopathic facial aseptic granuloma – an uncommon condition sometimes mistaken for unusually early acne – is actually often an expression of childhood rosacea.

"If you see these atypical skin lesions that look like acne cysts in young children who also have facial flushing, erythema, and perhaps pustules without comedones, be sure to look carefully at the eyes. Many times, they will have ocular rosacea with recurrent chalazions, conjunctival hyperemia, or keratitis. And if you think it’s ocular rosacea, you may want to make a referral to ophthalmology for assistance with ocular rosacea management," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"I find that many times oral antibiotics are highly useful in this subset," added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and professor of clinical pediatrics and medicine at the University of California, San Diego.

The pathogenesis of idiopathic facial aseptic granuloma (IFAG) is poorly understood. French dermatologists were first to identify the link between IFAG and rosacea. In a multicenter study involving 20 girls and 18 boys with IFAG, the investigators determined that 16 of the children, or 42%, met two or more criteria for rosacea (Pediatr. Dermatol. 2013;30:429-32).

Median age at diagnosis of IFAG was 43 months, and the children were subsequently followed for a median of 3.9 years before their evaluation for possible rosacea. Eleven of the 32 (34%) children with a single IFAG lesion met criteria for childhood rosacea, as did 5 of the 6 (83%) children with multiple skin lesions.

"So be aware: Although rosacea is very uncommon in our preteens and teens, it can occur," Dr. Eichenfield observed.

He reported having served as a clinical investigator and/or consultant to Allergan, Galderma, GSK-Stiefel, and Medicis/Valeant.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Rosacea is generally thought of as a common adult disorder with onset typically at age 30-50 years. But recent evidence indicates it can occur during early childhood, too.

Idiopathic facial aseptic granuloma – an uncommon condition sometimes mistaken for unusually early acne – is actually often an expression of childhood rosacea.

"If you see these atypical skin lesions that look like acne cysts in young children who also have facial flushing, erythema, and perhaps pustules without comedones, be sure to look carefully at the eyes. Many times, they will have ocular rosacea with recurrent chalazions, conjunctival hyperemia, or keratitis. And if you think it’s ocular rosacea, you may want to make a referral to ophthalmology for assistance with ocular rosacea management," Dr. Lawrence F. Eichenfield said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"I find that many times oral antibiotics are highly useful in this subset," added Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and professor of clinical pediatrics and medicine at the University of California, San Diego.

The pathogenesis of idiopathic facial aseptic granuloma (IFAG) is poorly understood. French dermatologists were first to identify the link between IFAG and rosacea. In a multicenter study involving 20 girls and 18 boys with IFAG, the investigators determined that 16 of the children, or 42%, met two or more criteria for rosacea (Pediatr. Dermatol. 2013;30:429-32).

Median age at diagnosis of IFAG was 43 months, and the children were subsequently followed for a median of 3.9 years before their evaluation for possible rosacea. Eleven of the 32 (34%) children with a single IFAG lesion met criteria for childhood rosacea, as did 5 of the 6 (83%) children with multiple skin lesions.

"So be aware: Although rosacea is very uncommon in our preteens and teens, it can occur," Dr. Eichenfield observed.

He reported having served as a clinical investigator and/or consultant to Allergan, Galderma, GSK-Stiefel, and Medicis/Valeant.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com