Bruce Jancin

COPENHAGEN – An ultrasmall yet highly potent single-chain antibody fragment directed against tumor necrosis factor–alpha showed promise for the treatment of Behçet’s disease flares in a pilot phase II study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We believe that we have something in our hands that may make a difference to these patients. Further development with follow-up studies is planned,” said Dr. Thomas Jung, chief medical officer at Delenex Therapeutics.

The agent, known for now as DLX105, utilizes the company’s proprietary PentraBody platform. DLX105 inhibits soluble as well as membrane-bound TNF-alpha. Because the protein antibody is so small, it has the capacity to penetrate into inflamed tissue, be it skin or cartilage. DLX105 is also being explored as a potential therapy for other flaring inflammatory skin and autoimmune disorders, he added.

“The antibody also leaves the tissue very rapidly. It doesn’t stick around as long as an IgG antibody. The typical half-life of this molecule is about 1 day. We believe this is actually an advantage when we talk about treating a flaring disease such as Behçet’s, where we want exposure for a certain time frame, but we don’t want to overexpose the patient over weeks and months when it is not really necessary,” Dr. Jung explained.

Behçet’s disease is a chronic autoimmune vasculitic disease which presents most often as oral ulcers, papulopustular skin lesions, genital ulcers, uveitis, and/or arthritis. Cardiac, gastrointestinal, and CNS involvement occurs less frequently. The pathogenesis of the disease is unknown; no specific cause or triggers have been identified. Behçet’s disease affects an estimated 20,000 people in the United States, but is far more common in Turkey, the Middle East, and Asia. All treatment is off-label; there is no approved therapy for Behçet’s disease. The most widely used agents are corticosteroids, colchicine, and cyclosporine, with the biologic TNF inhibitors often being utilized in an effort to prevent blindness when uveitis occurs.

Dr. Jung presented results of the small phase II open-label study, which involved six patients with Behçet’s disease for a mean of 10 years. All presented with a disease flare. All six had oral aphthous ulcers, four had skin lesions, three had joint pain, two had erythema nodosum, and one had genital ulcers. All participants received a single intravenous infusion of DLX105 at 10 mg/kg.

All of the oral ulcers healed within 1 week following the single dose of DLX105. Patients with joint pain reported it was substantially improved within 1-2 days after treatment. Genital lesions healed completely within 2 weeks. The skin lesions were also markedly improved. The clinical improvement was maintained up to 4 weeks post treatment.

The improvement in joint symptoms was not unexpected. DLX105 has been shown to inhibit human TNF-alpha–induced joint swelling in rats with an efficacy comparable to infliximab (Remicade), according to Dr. Jung.

Perhaps most impressively, Dr. Jung observed, erythema nodosum healed completely in both affected patients. Erythema nodosum can be notoriously difficult to treat. Indeed, one of the patients had erythema nodosum for 5 years during which multiple systemic therapies were employed without benefit.

bjancin@frontlinemedcom.com

COPENHAGEN – An ultrasmall yet highly potent single-chain antibody fragment directed against tumor necrosis factor–alpha showed promise for the treatment of Behçet’s disease flares in a pilot phase II study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We believe that we have something in our hands that may make a difference to these patients. Further development with follow-up studies is planned,” said Dr. Thomas Jung, chief medical officer at Delenex Therapeutics.

The agent, known for now as DLX105, utilizes the company’s proprietary PentraBody platform. DLX105 inhibits soluble as well as membrane-bound TNF-alpha. Because the protein antibody is so small, it has the capacity to penetrate into inflamed tissue, be it skin or cartilage. DLX105 is also being explored as a potential therapy for other flaring inflammatory skin and autoimmune disorders, he added.

“The antibody also leaves the tissue very rapidly. It doesn’t stick around as long as an IgG antibody. The typical half-life of this molecule is about 1 day. We believe this is actually an advantage when we talk about treating a flaring disease such as Behçet’s, where we want exposure for a certain time frame, but we don’t want to overexpose the patient over weeks and months when it is not really necessary,” Dr. Jung explained.

Behçet’s disease is a chronic autoimmune vasculitic disease which presents most often as oral ulcers, papulopustular skin lesions, genital ulcers, uveitis, and/or arthritis. Cardiac, gastrointestinal, and CNS involvement occurs less frequently. The pathogenesis of the disease is unknown; no specific cause or triggers have been identified. Behçet’s disease affects an estimated 20,000 people in the United States, but is far more common in Turkey, the Middle East, and Asia. All treatment is off-label; there is no approved therapy for Behçet’s disease. The most widely used agents are corticosteroids, colchicine, and cyclosporine, with the biologic TNF inhibitors often being utilized in an effort to prevent blindness when uveitis occurs.

Dr. Jung presented results of the small phase II open-label study, which involved six patients with Behçet’s disease for a mean of 10 years. All presented with a disease flare. All six had oral aphthous ulcers, four had skin lesions, three had joint pain, two had erythema nodosum, and one had genital ulcers. All participants received a single intravenous infusion of DLX105 at 10 mg/kg.

All of the oral ulcers healed within 1 week following the single dose of DLX105. Patients with joint pain reported it was substantially improved within 1-2 days after treatment. Genital lesions healed completely within 2 weeks. The skin lesions were also markedly improved. The clinical improvement was maintained up to 4 weeks post treatment.

The improvement in joint symptoms was not unexpected. DLX105 has been shown to inhibit human TNF-alpha–induced joint swelling in rats with an efficacy comparable to infliximab (Remicade), according to Dr. Jung.

Perhaps most impressively, Dr. Jung observed, erythema nodosum healed completely in both affected patients. Erythema nodosum can be notoriously difficult to treat. Indeed, one of the patients had erythema nodosum for 5 years during which multiple systemic therapies were employed without benefit.

bjancin@frontlinemedcom.com

COPENHAGEN – An ultrasmall yet highly potent single-chain antibody fragment directed against tumor necrosis factor–alpha showed promise for the treatment of Behçet’s disease flares in a pilot phase II study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We believe that we have something in our hands that may make a difference to these patients. Further development with follow-up studies is planned,” said Dr. Thomas Jung, chief medical officer at Delenex Therapeutics.

The agent, known for now as DLX105, utilizes the company’s proprietary PentraBody platform. DLX105 inhibits soluble as well as membrane-bound TNF-alpha. Because the protein antibody is so small, it has the capacity to penetrate into inflamed tissue, be it skin or cartilage. DLX105 is also being explored as a potential therapy for other flaring inflammatory skin and autoimmune disorders, he added.

“The antibody also leaves the tissue very rapidly. It doesn’t stick around as long as an IgG antibody. The typical half-life of this molecule is about 1 day. We believe this is actually an advantage when we talk about treating a flaring disease such as Behçet’s, where we want exposure for a certain time frame, but we don’t want to overexpose the patient over weeks and months when it is not really necessary,” Dr. Jung explained.

Behçet’s disease is a chronic autoimmune vasculitic disease which presents most often as oral ulcers, papulopustular skin lesions, genital ulcers, uveitis, and/or arthritis. Cardiac, gastrointestinal, and CNS involvement occurs less frequently. The pathogenesis of the disease is unknown; no specific cause or triggers have been identified. Behçet’s disease affects an estimated 20,000 people in the United States, but is far more common in Turkey, the Middle East, and Asia. All treatment is off-label; there is no approved therapy for Behçet’s disease. The most widely used agents are corticosteroids, colchicine, and cyclosporine, with the biologic TNF inhibitors often being utilized in an effort to prevent blindness when uveitis occurs.

Dr. Jung presented results of the small phase II open-label study, which involved six patients with Behçet’s disease for a mean of 10 years. All presented with a disease flare. All six had oral aphthous ulcers, four had skin lesions, three had joint pain, two had erythema nodosum, and one had genital ulcers. All participants received a single intravenous infusion of DLX105 at 10 mg/kg.

All of the oral ulcers healed within 1 week following the single dose of DLX105. Patients with joint pain reported it was substantially improved within 1-2 days after treatment. Genital lesions healed completely within 2 weeks. The skin lesions were also markedly improved. The clinical improvement was maintained up to 4 weeks post treatment.

The improvement in joint symptoms was not unexpected. DLX105 has been shown to inhibit human TNF-alpha–induced joint swelling in rats with an efficacy comparable to infliximab (Remicade), according to Dr. Jung.

Perhaps most impressively, Dr. Jung observed, erythema nodosum healed completely in both affected patients. Erythema nodosum can be notoriously difficult to treat. Indeed, one of the patients had erythema nodosum for 5 years during which multiple systemic therapies were employed without benefit.

bjancin@frontlinemedcom.com

COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.

He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.

Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.

“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.

In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.

Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.

In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.

A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.

A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.

Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.

Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).

In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).

Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.

An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.

Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.

COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.

He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.

Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.

“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.

In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.

Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.

In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.

A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.

A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.

Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.

Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).

In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).

Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.

An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.

Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.

COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.

He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.

Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.

“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.

In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.

Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.

In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.

A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.

A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.

Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.

Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).

In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).

Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.

An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.

Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.

COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.

He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.

Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.

“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.

In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.

Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.

In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.

A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.

A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.

Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.

Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).

In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).

Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.

An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.

Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.

bjancin@frontlinemedcom.com

COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.

He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.

Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.

“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.

In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.

Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.

In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.

A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.

A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.

Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.

Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).

In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).

Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.

An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.

Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.

bjancin@frontlinemedcom.com

COPENHAGEN – The increased risk of MI and stroke in patients who develop psoriasis as young adults is essentially confined to those having a positive family history of cardiovascular disease, according to a Danish national study presented at the annual congress of the European Academy of Dermatology and Venereology.

“We found a significantly increased risk of MACE [major adverse cardiovascular events] in patients with psoriasis only when a family history of cardiovascular disease was present. This just highlights why it’s important that future studies of cardiovascular risk in psoriasis should include family history. Also, an increased focus on cardiovascular disease in relatives may be appropriate in the cardiovascular risk assessment of patients with psoriasis,” said Dr. Alexander Egeberg of the University of Copenhagen.

He presented a population-based study involving 15 years of follow-up of 30,278 Danes diagnosed with psoriasis in their 20s and a control group consisting of nearly 2.7 million of their Danish contemporaries who were not. None had personal history of acute MI or stroke at baseline. Family medical history, including whether cardiovascular disease occurred in first-degree relatives, was available for all subjects.

Dr. Egeberg and coinvestigators mapped the incidence of acute MI, ischemic stroke, or cardiovascular death in psoriasis patients and the general population controls during follow-up.

“When you look at the patients who developed psoriasis and didn’t have a positive family history of cardiovascular disease, there are almost no cardiovascular events for the entire country,” Dr. Egeberg observed.

In contrast, in a multivariate analysis adjusted for age, gender, socioeconomic status, comorbid cardiovascular disease, smoking, and the use of cardiovascular medications, patients with mild psoriasis and a positive family history for cardiovascular disease had a 28% greater risk of a premature cardiovascular event than the general population during follow-up out to roughly age 40. Those with a positive family history and severe psoriasis as defined by the use of systemic therapies had a 62% increase in risk. Both of these elevated risks were statistically significant.

Among young adult Danes with a positive family history for cardiovascular disease, there were 222 MACE events during 62,225 person-years of follow-up in the mild psoriasis group and 31 events during 6,848 person-years in the 4,504 subjects with severe psoriasis. The resultant incidence rates in both groups were significantly higher than in the control group, who experienced 28,846 MACE events during 16.1 million person-years of follow-up.

In contrast, fewer than 10 MACE events occurred in Danish psoriasis patients without a family history of cardiovascular disease.

A positive family history was also associated with increased MACE in the nonpsoriatic general population, although it didn’t confer as great a risk as in the Danes with psoriasis.

A point worthy of consideration, Dr. Egeberg noted, is that the epidemiology of psoriasis in Denmark apparently differs in several important ways from psoriasis in the United States and some other countries. For one, the prevalence is higher in Scandinavian countries – 7.1% in a Danish national cross-sectional study (Int J Dermatol. 2013 Jun;52[6]:681-3) and 8% in neighboring Norway – as compared with 2%-3% in much of the rest of the world.

Moreover, according to the same cross-sectional study, the prevalence of traditional cardiovascular risk factors, such as smoking and the components of the metabolic syndrome, isn’t higher in Danish psoriasis patients than in the country’s general population. That’s in contrast to the situation in the United Kingdom, where Dr. Joel M. Gelfand of the University of Pennsylvania and associates reported a decade ago in a landmark study that the prevalence of hypertension, obesity, hyperlipidemia, diabetes, and smoking were all higher in persons with psoriasis than in the general population (J Am Acad Dermatol. 2006 Nov;55[5]:829-35). Similar findings were subsequently reported in U.S. psoriasis patients.

Despite their absence of elevated levels of the standard cardiovascular risk factors, Danish psoriasis patients as a group do face a clinically significant increase in cardiovascular risk, compared with the general population, as shown in yet another Danish national cohort study in which the rate ratios for cardiovascular death for mild and severe psoriasis were 1.14 and 1.57, respectively, compared with controls (J Intern Med. 2011 Aug;270[2]:147-57).

In an even more recent Danish nationwide study, the overall death rate was found to be 25.4 per 1,000 person-years in patients with severe psoriasis, 17.0 in those with mild psoriasis, and 13.8 per 1,000 person-years in the general population (J Eur Acad Dermatol Venereol. 2015 May;29[5]:1002-5).

Dr. Egeberg said his new Danish findings suggest that even in psoriasis patients with a greater burden of systemic inflammation as expressed in severe disease, that burden alone doesn’t translate into increased cardiovascular risk. Rather, elevated cardiovascular risk appears to be a consequence of heritable factors, Dr. Egeberg said.

An important caveat regarding this study, he continued, is that the mean age at which participants were diagnosed with psoriasis was 26.6 years. It’s unclear whether the study findings extend to individuals who develop the dermatologic disease later in life.

Dr. Egeberg reported having no financial conflicts regarding this study, supported by Danish national research funding.

bjancin@frontlinemedcom.com

COPENHAGEN – An oral small molecule with a novel mechanism of action for treatment of moderate to severe plaque psoriasis is being developed as a potential first-line systemic treatment in view of its highly favorable safety profile.

The investigational drug, known for now as CF101, is a first-in-class agonist of the A3 adenosine receptor. This cell surface receptor is upregulated in the pathologic cells of certain inflammatory diseases, but has little or no expression in normal cells. This high degree of specificity accounts for its safety, which in a recent phase II/III trial was essentially indistinguishable from placebo, making it an attractive potential alternative to methotrexate or biologics as a starting point in systemic therapy, Pnina Fishman, Ph.D., said at the annual congress of the European Academy of Dermatology and Venereology.

Planning is underway for a pivotal phase III trial of CF101 in psoriasis, which is also being organized for CF101 in rheumatoid arthritis on the strength of favorable phase II findings, according to Dr. Fishman, CEO of Can-Fite BioPharma, an Israeli biotech company that is developing the drug.

The phase II/III psoriasis trial was a 326-patient, double-blind, placebo-controlled study. It showed efficacy comparable to and in some respects better than that reported in the phase III ESTEEM-1 study of the oral phosphodiesterase 4 inhibitor apremilast (J Am Acad Dermatol. 2015 Jul;73:37-49).

Moreover, it appears that the twice-daily 2-mg dosing of CF101 studied in the phase II/III trial was suboptimal in light of the observed linear increase in Psoriasis Area and Severity Index (PASI)-75, -90, and -100 response rates over time. Those response rates rose steadily until the study’s end at week 32 with no evidence of a plateau. In contrast, in ESTEEM-1, the improvement with apremilast (Otezla) leveled off starting at about week 20, she observed.

In the recent phase II/III trial, the PASI-75 rate for CF101 at week 12 – the prespecified primary endpoint – was not significantly better than placebo was. However, the PASI-75 response rate continued to climb such that by week 32, it was 35.3%, similar to the 33.1% PASI-75 response seen at 16 weeks in ESTEEM-1. PASI improved by an average of 57% from baseline to week 32 with CF101 with no plateau in sight, and by 55% with apremilast at week 16, with a leveling off at week 20. This is why the upcoming phase III trial will employ a higher dose of CF101 than twice-daily 2-mg dose used in the phase II/III study and will run longer. The goal is to achieve higher PASI response rates faster than obtainable with 2 mg BID, Dr. Fishman explained.

She added that the PASI-90 response data in the phase II/III trial bode particularly well for the future of CF101 as a first-line systemic agent. At week 32, this stringent outcome measure was achieved by 26.9% of participants who hadn’t previously been on methotrexate or a biologic and by 13.7% of those who had. And as was the case for the PASI-75 results, the PASI-90 response increased in linear fashion out to 32 weeks with no plateau. In ESTEEM-1, the PASI-90 rate was 9.8% at week 16.

No treatment-related adverse events were seen in the phase II/III CF101 study, Dr. Fishman reported.

The study was sponsored by Can-Fite BioPharma and presented by Dr. Fishman, who is the company’s CEO.

bjancin@frontlinemedcom.com

COPENHAGEN – An oral small molecule with a novel mechanism of action for treatment of moderate to severe plaque psoriasis is being developed as a potential first-line systemic treatment in view of its highly favorable safety profile.

The investigational drug, known for now as CF101, is a first-in-class agonist of the A3 adenosine receptor. This cell surface receptor is upregulated in the pathologic cells of certain inflammatory diseases, but has little or no expression in normal cells. This high degree of specificity accounts for its safety, which in a recent phase II/III trial was essentially indistinguishable from placebo, making it an attractive potential alternative to methotrexate or biologics as a starting point in systemic therapy, Pnina Fishman, Ph.D., said at the annual congress of the European Academy of Dermatology and Venereology.

Planning is underway for a pivotal phase III trial of CF101 in psoriasis, which is also being organized for CF101 in rheumatoid arthritis on the strength of favorable phase II findings, according to Dr. Fishman, CEO of Can-Fite BioPharma, an Israeli biotech company that is developing the drug.

The phase II/III psoriasis trial was a 326-patient, double-blind, placebo-controlled study. It showed efficacy comparable to and in some respects better than that reported in the phase III ESTEEM-1 study of the oral phosphodiesterase 4 inhibitor apremilast (J Am Acad Dermatol. 2015 Jul;73:37-49).

Moreover, it appears that the twice-daily 2-mg dosing of CF101 studied in the phase II/III trial was suboptimal in light of the observed linear increase in Psoriasis Area and Severity Index (PASI)-75, -90, and -100 response rates over time. Those response rates rose steadily until the study’s end at week 32 with no evidence of a plateau. In contrast, in ESTEEM-1, the improvement with apremilast (Otezla) leveled off starting at about week 20, she observed.

In the recent phase II/III trial, the PASI-75 rate for CF101 at week 12 – the prespecified primary endpoint – was not significantly better than placebo was. However, the PASI-75 response rate continued to climb such that by week 32, it was 35.3%, similar to the 33.1% PASI-75 response seen at 16 weeks in ESTEEM-1. PASI improved by an average of 57% from baseline to week 32 with CF101 with no plateau in sight, and by 55% with apremilast at week 16, with a leveling off at week 20. This is why the upcoming phase III trial will employ a higher dose of CF101 than twice-daily 2-mg dose used in the phase II/III study and will run longer. The goal is to achieve higher PASI response rates faster than obtainable with 2 mg BID, Dr. Fishman explained.

She added that the PASI-90 response data in the phase II/III trial bode particularly well for the future of CF101 as a first-line systemic agent. At week 32, this stringent outcome measure was achieved by 26.9% of participants who hadn’t previously been on methotrexate or a biologic and by 13.7% of those who had. And as was the case for the PASI-75 results, the PASI-90 response increased in linear fashion out to 32 weeks with no plateau. In ESTEEM-1, the PASI-90 rate was 9.8% at week 16.

No treatment-related adverse events were seen in the phase II/III CF101 study, Dr. Fishman reported.

The study was sponsored by Can-Fite BioPharma and presented by Dr. Fishman, who is the company’s CEO.

bjancin@frontlinemedcom.com

COPENHAGEN – An oral small molecule with a novel mechanism of action for treatment of moderate to severe plaque psoriasis is being developed as a potential first-line systemic treatment in view of its highly favorable safety profile.

The investigational drug, known for now as CF101, is a first-in-class agonist of the A3 adenosine receptor. This cell surface receptor is upregulated in the pathologic cells of certain inflammatory diseases, but has little or no expression in normal cells. This high degree of specificity accounts for its safety, which in a recent phase II/III trial was essentially indistinguishable from placebo, making it an attractive potential alternative to methotrexate or biologics as a starting point in systemic therapy, Pnina Fishman, Ph.D., said at the annual congress of the European Academy of Dermatology and Venereology.

Planning is underway for a pivotal phase III trial of CF101 in psoriasis, which is also being organized for CF101 in rheumatoid arthritis on the strength of favorable phase II findings, according to Dr. Fishman, CEO of Can-Fite BioPharma, an Israeli biotech company that is developing the drug.

The phase II/III psoriasis trial was a 326-patient, double-blind, placebo-controlled study. It showed efficacy comparable to and in some respects better than that reported in the phase III ESTEEM-1 study of the oral phosphodiesterase 4 inhibitor apremilast (J Am Acad Dermatol. 2015 Jul;73:37-49).

Moreover, it appears that the twice-daily 2-mg dosing of CF101 studied in the phase II/III trial was suboptimal in light of the observed linear increase in Psoriasis Area and Severity Index (PASI)-75, -90, and -100 response rates over time. Those response rates rose steadily until the study’s end at week 32 with no evidence of a plateau. In contrast, in ESTEEM-1, the improvement with apremilast (Otezla) leveled off starting at about week 20, she observed.

In the recent phase II/III trial, the PASI-75 rate for CF101 at week 12 – the prespecified primary endpoint – was not significantly better than placebo was. However, the PASI-75 response rate continued to climb such that by week 32, it was 35.3%, similar to the 33.1% PASI-75 response seen at 16 weeks in ESTEEM-1. PASI improved by an average of 57% from baseline to week 32 with CF101 with no plateau in sight, and by 55% with apremilast at week 16, with a leveling off at week 20. This is why the upcoming phase III trial will employ a higher dose of CF101 than twice-daily 2-mg dose used in the phase II/III study and will run longer. The goal is to achieve higher PASI response rates faster than obtainable with 2 mg BID, Dr. Fishman explained.

She added that the PASI-90 response data in the phase II/III trial bode particularly well for the future of CF101 as a first-line systemic agent. At week 32, this stringent outcome measure was achieved by 26.9% of participants who hadn’t previously been on methotrexate or a biologic and by 13.7% of those who had. And as was the case for the PASI-75 results, the PASI-90 response increased in linear fashion out to 32 weeks with no plateau. In ESTEEM-1, the PASI-90 rate was 9.8% at week 16.

No treatment-related adverse events were seen in the phase II/III CF101 study, Dr. Fishman reported.

The study was sponsored by Can-Fite BioPharma and presented by Dr. Fishman, who is the company’s CEO.

bjancin@frontlinemedcom.com

ORLANDO – Moderate aerobic exercise and a more intensive regimen proved equally effective in reducing intrahepatic triglyceride content in centrally obese patients with nonalcoholic fatty liver disease in a 12-month randomized, controlled trial.

However, the more intensive exercise program had the edge in terms of favorable impact on metabolic risk factors. While both exercise prescriptions reduced body weight and blood pressure to a similar extent over the course of 12 months, the intensive-exercise group showed bigger reductions in body fat mass, visceral fat, and subcutaneous fat (see graphic), Dr. Hui-Jie Zhang of Xiamen (China) University said at the American Heart Association scientific sessions.

The observer-blinded study included 220 middle-age Chinese patients with central obesity and confirmed nonalcoholic fatty liver disease (NAFLD), a common risk factor for cardiovascular disease. They were randomized to three groups: a moderate exercise program that consisted of brisk walking for 150 minutes per week for 12 months; an intensive exercise regimen involving 30 minutes of treadmill running at 65%-80% of maximum oxygen consumption 5 days per week for 6 months, followed by 6 months of brisk walking on the same schedule as the moderate exercise group; or a usual-care control group that received lifestyle counseling.

The primary endpoint was change in intrahepatic triglyceride content as measured by proton magnetic resonance spectroscopy at 12 months. It was reduced from baseline by 6.45% in the intensive exercise group and similarly by 6.19% with moderate exercise, both significantly greater effects than the 2.85% decrease in the control group.

Dr. Zhang reported having no financial conflicts of interest regarding this study.

ORLANDO – Moderate aerobic exercise and a more intensive regimen proved equally effective in reducing intrahepatic triglyceride content in centrally obese patients with nonalcoholic fatty liver disease in a 12-month randomized, controlled trial.

However, the more intensive exercise program had the edge in terms of favorable impact on metabolic risk factors. While both exercise prescriptions reduced body weight and blood pressure to a similar extent over the course of 12 months, the intensive-exercise group showed bigger reductions in body fat mass, visceral fat, and subcutaneous fat (see graphic), Dr. Hui-Jie Zhang of Xiamen (China) University said at the American Heart Association scientific sessions.

The observer-blinded study included 220 middle-age Chinese patients with central obesity and confirmed nonalcoholic fatty liver disease (NAFLD), a common risk factor for cardiovascular disease. They were randomized to three groups: a moderate exercise program that consisted of brisk walking for 150 minutes per week for 12 months; an intensive exercise regimen involving 30 minutes of treadmill running at 65%-80% of maximum oxygen consumption 5 days per week for 6 months, followed by 6 months of brisk walking on the same schedule as the moderate exercise group; or a usual-care control group that received lifestyle counseling.

The primary endpoint was change in intrahepatic triglyceride content as measured by proton magnetic resonance spectroscopy at 12 months. It was reduced from baseline by 6.45% in the intensive exercise group and similarly by 6.19% with moderate exercise, both significantly greater effects than the 2.85% decrease in the control group.

Dr. Zhang reported having no financial conflicts of interest regarding this study.

ORLANDO – Moderate aerobic exercise and a more intensive regimen proved equally effective in reducing intrahepatic triglyceride content in centrally obese patients with nonalcoholic fatty liver disease in a 12-month randomized, controlled trial.

However, the more intensive exercise program had the edge in terms of favorable impact on metabolic risk factors. While both exercise prescriptions reduced body weight and blood pressure to a similar extent over the course of 12 months, the intensive-exercise group showed bigger reductions in body fat mass, visceral fat, and subcutaneous fat (see graphic), Dr. Hui-Jie Zhang of Xiamen (China) University said at the American Heart Association scientific sessions.

The observer-blinded study included 220 middle-age Chinese patients with central obesity and confirmed nonalcoholic fatty liver disease (NAFLD), a common risk factor for cardiovascular disease. They were randomized to three groups: a moderate exercise program that consisted of brisk walking for 150 minutes per week for 12 months; an intensive exercise regimen involving 30 minutes of treadmill running at 65%-80% of maximum oxygen consumption 5 days per week for 6 months, followed by 6 months of brisk walking on the same schedule as the moderate exercise group; or a usual-care control group that received lifestyle counseling.

The primary endpoint was change in intrahepatic triglyceride content as measured by proton magnetic resonance spectroscopy at 12 months. It was reduced from baseline by 6.45% in the intensive exercise group and similarly by 6.19% with moderate exercise, both significantly greater effects than the 2.85% decrease in the control group.

Dr. Zhang reported having no financial conflicts of interest regarding this study.

ORLANDO – Moderate aerobic exercise and a more intensive regimen proved equally effective in reducing intrahepatic triglyceride content in centrally obese patients with nonalcoholic fatty liver disease in a 12-month randomized, controlled trial.

However, the more intensive exercise program had the edge in terms of favorable impact on metabolic risk factors. While both exercise prescriptions reduced body weight and blood pressure to a similar extent over the course of 12 months, the intensive-exercise group showed bigger reductions in body fat mass, visceral fat, and subcutaneous fat (see graphic), Dr. Hui-Jie Zhang of Xiamen (China) University said at the American Heart Association scientific sessions.

The observer-blinded study included 220 middle-age Chinese patients with central obesity and confirmed nonalcoholic fatty liver disease (NAFLD), a common risk factor for cardiovascular disease. They were randomized to three groups: a moderate exercise program that consisted of brisk walking for 150 minutes per week for 12 months; an intensive exercise regimen involving 30 minutes of treadmill running at 65%-80% of maximum oxygen consumption 5 days per week for 6 months, followed by 6 months of brisk walking on the same schedule as the moderate exercise group; or a usual-care control group that received lifestyle counseling.

The primary endpoint was change in intrahepatic triglyceride content as measured by proton magnetic resonance spectroscopy at 12 months. It was reduced from baseline by 6.45% in the intensive exercise group and similarly by 6.19% with moderate exercise, both significantly greater effects than the 2.85% decrease in the control group.

Dr. Zhang reported having no financial conflicts of interest regarding this study.

bjancin@frontlinemedcom.com

ORLANDO – Moderate aerobic exercise and a more intensive regimen proved equally effective in reducing intrahepatic triglyceride content in centrally obese patients with nonalcoholic fatty liver disease in a 12-month randomized, controlled trial.

However, the more intensive exercise program had the edge in terms of favorable impact on metabolic risk factors. While both exercise prescriptions reduced body weight and blood pressure to a similar extent over the course of 12 months, the intensive-exercise group showed bigger reductions in body fat mass, visceral fat, and subcutaneous fat (see graphic), Dr. Hui-Jie Zhang of Xiamen (China) University said at the American Heart Association scientific sessions.

The observer-blinded study included 220 middle-age Chinese patients with central obesity and confirmed nonalcoholic fatty liver disease (NAFLD), a common risk factor for cardiovascular disease. They were randomized to three groups: a moderate exercise program that consisted of brisk walking for 150 minutes per week for 12 months; an intensive exercise regimen involving 30 minutes of treadmill running at 65%-80% of maximum oxygen consumption 5 days per week for 6 months, followed by 6 months of brisk walking on the same schedule as the moderate exercise group; or a usual-care control group that received lifestyle counseling.

The primary endpoint was change in intrahepatic triglyceride content as measured by proton magnetic resonance spectroscopy at 12 months. It was reduced from baseline by 6.45% in the intensive exercise group and similarly by 6.19% with moderate exercise, both significantly greater effects than the 2.85% decrease in the control group.

Dr. Zhang reported having no financial conflicts of interest regarding this study.

bjancin@frontlinemedcom.com

ORLANDO – Moderate aerobic exercise and a more intensive regimen proved equally effective in reducing intrahepatic triglyceride content in centrally obese patients with nonalcoholic fatty liver disease in a 12-month randomized, controlled trial.

However, the more intensive exercise program had the edge in terms of favorable impact on metabolic risk factors. While both exercise prescriptions reduced body weight and blood pressure to a similar extent over the course of 12 months, the intensive-exercise group showed bigger reductions in body fat mass, visceral fat, and subcutaneous fat (see graphic), Dr. Hui-Jie Zhang of Xiamen (China) University said at the American Heart Association scientific sessions.

The observer-blinded study included 220 middle-age Chinese patients with central obesity and confirmed nonalcoholic fatty liver disease (NAFLD), a common risk factor for cardiovascular disease. They were randomized to three groups: a moderate exercise program that consisted of brisk walking for 150 minutes per week for 12 months; an intensive exercise regimen involving 30 minutes of treadmill running at 65%-80% of maximum oxygen consumption 5 days per week for 6 months, followed by 6 months of brisk walking on the same schedule as the moderate exercise group; or a usual-care control group that received lifestyle counseling.

The primary endpoint was change in intrahepatic triglyceride content as measured by proton magnetic resonance spectroscopy at 12 months. It was reduced from baseline by 6.45% in the intensive exercise group and similarly by 6.19% with moderate exercise, both significantly greater effects than the 2.85% decrease in the control group.

Dr. Zhang reported having no financial conflicts of interest regarding this study.

bjancin@frontlinemedcom.com

ORLANDO – Subclinical elevated maternal blood glucose levels during the second trimester are strongly associated with increased risk of tetralogy of Fallot, Dr. James R. Priest reported at the American Heart Association scientific sessions.

It’s well established that maternal type 2 diabetes and gestational diabetes are strong maternal risk factors for structural congenital heart disease in their offspring. But the women in this study didn’t meet criteria for those diagnoses. They were asymptomatic, and their elevations in blood glucose in random nonfasting measurements obtained in the second trimester were below the 200 mg/dL threshold.

©Petro Feketa/iStockphoto.com

Thus, this study provides the first evidence that maternal blood glucose as a continuous variable is associated with increased risk of specific congenital heart defects in offspring, according to Dr. Priest, a pediatric cardiologist at Stanford (Calif.) University.

Of note, in this study of nondiabetic women, an elevated blood glucose was not associated with increased risk of d-transposition of the great arteries (dTGA), which, like tetralogy of Fallot, has been associated with maternal diabetes.

Dr. Priest presented an observational study of 277 pregnant, nondiabetic women, of whom 55 gave birth to a baby with tetralogy of Fallot, 42 had a baby with dTGA, and 180 gave birth to a baby without congenital heart disease or other malformations. Random nonfasting blood glucose and serum insulin levels were obtained from all subjects during weeks 15-18 of pregnancy.

The median maternal blood glucose level was 91.5 mg/dL in controls, similar at 90 mg/dL in the mothers of infants with dTGA, and significantly increased at 97 mg/dL in the mothers of offspring with tetralogy of Fallot. In a multivariate analysis adjusted for maternal age and ethnicity, elevated nonfasting second-trimester maternal glucose was associated with a 7.54-fold increased risk of having an infant with tetralogy of Fallot.

Maternal serum insulin level wasn’t associated with the risk of congenital heart disease.

Dr. Priest emphasized that while this study breaks new ground, the findings must be considered preliminary.

“Maternal blood glucose levels are influenced by diet, exercise, beta-cell function, and insulin resistance. Thus, blood glucose levels may simply be a marker of risk conferred by another physiologic process. The question remains whether elevated blood glucose or a variety of correlated but independent traits is behind the observed association,” he noted.

He plans to answer this key question by studying the relationship between these physiologic traits and blood glucose levels earlier in pregnancy.

This study was funded by the Stanford Cardiovascular Institute and the National Institutes of Health. Dr. Priest reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ORLANDO – Subclinical elevated maternal blood glucose levels during the second trimester are strongly associated with increased risk of tetralogy of Fallot, Dr. James R. Priest reported at the American Heart Association scientific sessions.

It’s well established that maternal type 2 diabetes and gestational diabetes are strong maternal risk factors for structural congenital heart disease in their offspring. But the women in this study didn’t meet criteria for those diagnoses. They were asymptomatic, and their elevations in blood glucose in random nonfasting measurements obtained in the second trimester were below the 200 mg/dL threshold.

©Petro Feketa/iStockphoto.com

Thus, this study provides the first evidence that maternal blood glucose as a continuous variable is associated with increased risk of specific congenital heart defects in offspring, according to Dr. Priest, a pediatric cardiologist at Stanford (Calif.) University.

Of note, in this study of nondiabetic women, an elevated blood glucose was not associated with increased risk of d-transposition of the great arteries (dTGA), which, like tetralogy of Fallot, has been associated with maternal diabetes.

Dr. Priest presented an observational study of 277 pregnant, nondiabetic women, of whom 55 gave birth to a baby with tetralogy of Fallot, 42 had a baby with dTGA, and 180 gave birth to a baby without congenital heart disease or other malformations. Random nonfasting blood glucose and serum insulin levels were obtained from all subjects during weeks 15-18 of pregnancy.

The median maternal blood glucose level was 91.5 mg/dL in controls, similar at 90 mg/dL in the mothers of infants with dTGA, and significantly increased at 97 mg/dL in the mothers of offspring with tetralogy of Fallot. In a multivariate analysis adjusted for maternal age and ethnicity, elevated nonfasting second-trimester maternal glucose was associated with a 7.54-fold increased risk of having an infant with tetralogy of Fallot.

Maternal serum insulin level wasn’t associated with the risk of congenital heart disease.

Dr. Priest emphasized that while this study breaks new ground, the findings must be considered preliminary.

“Maternal blood glucose levels are influenced by diet, exercise, beta-cell function, and insulin resistance. Thus, blood glucose levels may simply be a marker of risk conferred by another physiologic process. The question remains whether elevated blood glucose or a variety of correlated but independent traits is behind the observed association,” he noted.

He plans to answer this key question by studying the relationship between these physiologic traits and blood glucose levels earlier in pregnancy.

This study was funded by the Stanford Cardiovascular Institute and the National Institutes of Health. Dr. Priest reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ORLANDO – Subclinical elevated maternal blood glucose levels during the second trimester are strongly associated with increased risk of tetralogy of Fallot, Dr. James R. Priest reported at the American Heart Association scientific sessions.

It’s well established that maternal type 2 diabetes and gestational diabetes are strong maternal risk factors for structural congenital heart disease in their offspring. But the women in this study didn’t meet criteria for those diagnoses. They were asymptomatic, and their elevations in blood glucose in random nonfasting measurements obtained in the second trimester were below the 200 mg/dL threshold.

©Petro Feketa/iStockphoto.com

Thus, this study provides the first evidence that maternal blood glucose as a continuous variable is associated with increased risk of specific congenital heart defects in offspring, according to Dr. Priest, a pediatric cardiologist at Stanford (Calif.) University.

Of note, in this study of nondiabetic women, an elevated blood glucose was not associated with increased risk of d-transposition of the great arteries (dTGA), which, like tetralogy of Fallot, has been associated with maternal diabetes.

Dr. Priest presented an observational study of 277 pregnant, nondiabetic women, of whom 55 gave birth to a baby with tetralogy of Fallot, 42 had a baby with dTGA, and 180 gave birth to a baby without congenital heart disease or other malformations. Random nonfasting blood glucose and serum insulin levels were obtained from all subjects during weeks 15-18 of pregnancy.

The median maternal blood glucose level was 91.5 mg/dL in controls, similar at 90 mg/dL in the mothers of infants with dTGA, and significantly increased at 97 mg/dL in the mothers of offspring with tetralogy of Fallot. In a multivariate analysis adjusted for maternal age and ethnicity, elevated nonfasting second-trimester maternal glucose was associated with a 7.54-fold increased risk of having an infant with tetralogy of Fallot.

Maternal serum insulin level wasn’t associated with the risk of congenital heart disease.

Dr. Priest emphasized that while this study breaks new ground, the findings must be considered preliminary.

“Maternal blood glucose levels are influenced by diet, exercise, beta-cell function, and insulin resistance. Thus, blood glucose levels may simply be a marker of risk conferred by another physiologic process. The question remains whether elevated blood glucose or a variety of correlated but independent traits is behind the observed association,” he noted.

He plans to answer this key question by studying the relationship between these physiologic traits and blood glucose levels earlier in pregnancy.

This study was funded by the Stanford Cardiovascular Institute and the National Institutes of Health. Dr. Priest reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com