Bruce Jancin

CHICAGO – The largest-ever randomized trial of catheter ablation for atrial fibrillation ended in a draw, but there may be a clear winner for some patients.

Safety and 1-year efficacy of radiofrequency ablation and cryoballoon ablation were roughly 65% in both treatment arms of the 769-patient Fire and Ice trial.

However, in an interview at the annual meeting of the American College of Cardiology, principal investigator Dr. Karl-Heinz Kuck of Asklepios Klinik St. Georg, Hamburg, Germany, explains why the results are actually a victory for cryoablation.

bjancin@frontlinemedcom.com

CHICAGO – The largest-ever randomized trial of catheter ablation for atrial fibrillation ended in a draw, but there may be a clear winner for some patients.

Safety and 1-year efficacy of radiofrequency ablation and cryoballoon ablation were roughly 65% in both treatment arms of the 769-patient Fire and Ice trial.

However, in an interview at the annual meeting of the American College of Cardiology, principal investigator Dr. Karl-Heinz Kuck of Asklepios Klinik St. Georg, Hamburg, Germany, explains why the results are actually a victory for cryoablation.

bjancin@frontlinemedcom.com

CHICAGO – The largest-ever randomized trial of catheter ablation for atrial fibrillation ended in a draw, but there may be a clear winner for some patients.

Safety and 1-year efficacy of radiofrequency ablation and cryoballoon ablation were roughly 65% in both treatment arms of the 769-patient Fire and Ice trial.

However, in an interview at the annual meeting of the American College of Cardiology, principal investigator Dr. Karl-Heinz Kuck of Asklepios Klinik St. Georg, Hamburg, Germany, explains why the results are actually a victory for cryoablation.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).

He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.

“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.

He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.

Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.

Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.

The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.

The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).

Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).

He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.

“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.

He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.

Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.

Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.

The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.

The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).

Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Intralesional injection of interferon alfa-2b is an excellent option for the treatment of large problematic basal cell carcinomas in patients who aren’t interested in the higher-morbidity options, Dr. David L. Swanson said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“This is a really effective way to treat basal cell carcinomas. These things just melt away before your eyes. It’s really quite amazing,” observed Dr. Swanson of Mayo Clinic Scottsdale (Ariz.).

He finds this therapy particularly useful in frail elderly patients who have a large BCC on the head or neck. A good example would be an 89-year-old with multiple comorbid conditions who has a 2-cm BCC on the tip of the nose and doesn’t want anything done about it. The patient declines the options of Mohs micrographic surgery or radiotherapy.

“This is the patient who just wants to be left alone. That’s fine if they’re going to be dead within a year, but if they’re going to be around for several years, that basal cell carcinoma could become a major issue for them,” the dermatologist continued.

He and his colleagues at the Mayo Clinic follow a treatment regimen similar to one laid out by Turkish investigators more than a decade ago in one of the few long-term outcome studies of intralesional interferon for treatment of BCCs.

Although interferon alfa-2b is approved for the intralesional treatment of genital warts and subcutaneously for Kaposi’s sarcoma and malignant melanoma, among other conditions, it’s off-label therapy for BCCs. The treatment entails thrice-weekly intralesional injections for 3 weeks. The dosing is 1.5 million units per injection for BCCs smaller than 2 cm and 3 million units per injection for BCCs that are 2 cm or larger. The injections are given without anesthesia, but premedication with 500-1,000 mg of acetaminophen is advisable to minimize aches and fever.

Interferon alfa-2b (Intron A) comes in a vial containing 10 million units with 1 mL of diluent. It’s important to reconstitute it carefully, similar to onabotulinumtoxin. Don’t shake it, Dr. Swanson advised.

The Turkish report included 20 patients with histopathologically proven BCCs on the head or neck. At clinical and dermatopathologic follow-up 8 weeks after the last interferon injection, 11 BCCs showed complete clinical and histopathologic cure, six showed partial remission, two showed no response, and one actually increased in size during treatment.

The 11 patients with an initial complete cure were followed for 7 years. During that period, only one of the 11 skin cancers recurred, at the fifth year (Clin Drug Investig. 2005;25[10]:661-7).

Dr. Swanson reported having no financial conflicts regarding his presentation. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

bjancin@frontlinemedcom.com

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

bjancin@frontlinemedcom.com

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

bjancin@frontlinemedcom.com

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

bjancin@frontlinemedcom.com

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

bjancin@frontlinemedcom.com

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

bjancin@frontlinemedcom.com

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

bjancin@frontlinemedcom.com

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

bjancin@frontlinemedcom.com

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

bjancin@frontlinemedcom.com

CHICAGO – The success in the HOPE-3 trial of a two-pronged strategy of a statin plus moderate-dose antihypertensive therapy has expanded the boundaries of primary preventive pharmacotherapy to incorporate many intermediate-cardiovascular-risk patients without cardiovascular disease.

In the Heart Outcomes Evaluation (HOPE)-3 trial, the combination of rosuvastatin (Crestor) at 10 mg/day plus antihypertensive therapy with 16 mg/day of candesartan and 12.5 mg/day of hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL-cholesterol and inflammatory biomarker levels. In nonhypertensive study participants, however, blood pressure-lowering therapy provided no added benefit beyond that achieved with the statin alone, which yielded a 25% relative risk reduction in cardiovascular events compared with placebo, Dr. Salim Yusuf reported at the annual meeting of the American College of Cardiology.

The HOPE-3 trial was the first formal study of the polypill concept of fixed-dose, low-dose combination therapy as a public health tool for primary prevention in an intermediate-risk population without cardiovascular disease. It’s a simple, low-cost, safe, pragmatic preventive strategy that doesn’t require baseline laboratory measurements, dose titration visits, or frequent safety monitoring, he noted.

“The original concept of the polypill was to give it to everyone over age 55. We found in HOPE-3 that the polypill concept is not valid for everybody. It demonstrated benefit in hypertensives but not in nonhypertensives, where a statin alone was beneficial,” said Dr. Yusuf, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“The clinical implication is that statins should be used much more widely than they currently are. Most guidelines for hypertension don’t say to give a statin. But HOPE-3 is saying hypertensives will benefit. About half of the 40% reduction in the risk of cardiovascular events we saw with combination therapy in patients in the highest third for baseline systolic blood pressure – that is, above 143.5 mm Hg, with a mean of 154 mm Hg – was due to the rosuvastatin and half to the antihypertensive therapy. Our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously,” he noted. Dr. Yusuf discussed the findings in a video interview.

The double-blind trial included a diverse population of 12,705 men age 55 or older and women age 65 or older in 21 countries. All were at intermediate cardiovascular risk by conventional stratification methods; none had a history of cardiovascular disease. They were randomized to rosuvastatin or placebo, dual antihypertensive therapy or placebo, or to all three medications or double placebo. The combined-therapy group experienced a 33.7 mg/dL greater drop in LDL-cholesterol and a 6.2 mm Hg bigger reduction in systolic blood pressure than in patients on dual placebo.

During a median followup of 5.6 years, the composite rate of cardiovascular death, nonfatal MI, or nonfatal stroke was 3.6% in the combined-therapy group and 5.0% with dual placebo, for a relative risk reduction of 29%. The number needed to treat for 5.6 years in order to prevent one event of the composite outcome was 72. However, the separation in the event rate curves for the two groups grew larger over time. With an additional planned followup of 3-5 years in HOPE-3, it’s likely the benefits will become even greater, according to Dr. Yusuf.

Combination therapy proved safe. Muscle aches and weakness as well as lightheadedness were more common in the combined treatment group than with dual placebo. However, permanent discontinuation rates were similar in the two groups.

HOPE-3 coinvestigator Dr. Eva Lonn presented the comparison between patients randomized to antihypertensive therapy without rosuvastatin or to placebo. In a prespecified subgroup analysis, active treatment resulted in a significant 27% reduction in the risk of the composite outcome compared with placebo in patients in the top one-third of baseline systolic blood pressure, no benefit in those with a systolic blood pressure of 131.6-143.5 mm Hg, and a suggestion of possible harm in patients whose systolic pressure at enrollment was 131.5 mm Hg or less.

Thus, the study helps define the minimum blood pressure at which antihypertensive therapy becomes beneficial, noted Dr. Lonn, professor of cardiology at McMaster University.

Dr. Yusuf said enthusiasm for the polypill concept as a means of reducing the growing global burden of cardiovascular disease remains strong among many experts. There is broad interest in a polypill for secondary prevention that will include aspirin, a beta blocker, and an ACE inhibitor of angiotensin receptor blocker as a low-cost means of improving medication adherence. And several large clinical trials of the polypill concept for primary prevention are underway, including a randomized trial conducted by Dr. Yusuf and coworkers in which several thousand high-risk subjects without baseline cardiovascular disease will receive a combination of a statin plus not two but three antihypertensive drugs.

Discussant Dr. Donald M. Lloyd-Jones commented, “What strikes me about HOPE-3 is that this is a population at risk, but not at particularly high risk.” And yet these patients benefited from statin therapy regardless of their baseline LDL, noted Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago, and an architect of the risk-based approach to statin use that’s a centerpiece of the current ACC/AHA guidelines on atherosclerotic cardiovascular risk reduction.

In an interview, Dr. Sidney C. Smith, Jr., said the HOPE-3 data are “worthy of consideration” as experts meet at ACC 16 to begin updating guidelines for the treatment of hypertension. In particular, the key findings that moderate-risk hypertensive patients benefited from a statin regardless of their baseline LDL and initiation of blood pressure-lowering therapy was beneficial for patients with a systolic blood pressure in the 140s but not in those with a systolic pressure in the 120s and 130s could be practice changing, according to Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.

Drs. Yusuf and Lonn reported receiving institutional research grants from the Canadian Institutes of Health Research and AstraZeneca, which funded the trial.

Simultaneous with the presentation of the HOPE-3 results at ACC 16 in Chicago, the study on cholesterol lowering and the study on blood pressure and cholesterol lowering led by Dr. Yusef as well as the study on blood pressure lowering led by Dr. Lonn were published online at NEJM.org.

bjancin@frontlinemedcom.com

CHICAGO – The success in the HOPE-3 trial of a two-pronged strategy of a statin plus moderate-dose antihypertensive therapy has expanded the boundaries of primary preventive pharmacotherapy to incorporate many intermediate-cardiovascular-risk patients without cardiovascular disease.

In the Heart Outcomes Evaluation (HOPE)-3 trial, the combination of rosuvastatin (Crestor) at 10 mg/day plus antihypertensive therapy with 16 mg/day of candesartan and 12.5 mg/day of hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL-cholesterol and inflammatory biomarker levels. In nonhypertensive study participants, however, blood pressure-lowering therapy provided no added benefit beyond that achieved with the statin alone, which yielded a 25% relative risk reduction in cardiovascular events compared with placebo, Dr. Salim Yusuf reported at the annual meeting of the American College of Cardiology.

The HOPE-3 trial was the first formal study of the polypill concept of fixed-dose, low-dose combination therapy as a public health tool for primary prevention in an intermediate-risk population without cardiovascular disease. It’s a simple, low-cost, safe, pragmatic preventive strategy that doesn’t require baseline laboratory measurements, dose titration visits, or frequent safety monitoring, he noted.

“The original concept of the polypill was to give it to everyone over age 55. We found in HOPE-3 that the polypill concept is not valid for everybody. It demonstrated benefit in hypertensives but not in nonhypertensives, where a statin alone was beneficial,” said Dr. Yusuf, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“The clinical implication is that statins should be used much more widely than they currently are. Most guidelines for hypertension don’t say to give a statin. But HOPE-3 is saying hypertensives will benefit. About half of the 40% reduction in the risk of cardiovascular events we saw with combination therapy in patients in the highest third for baseline systolic blood pressure – that is, above 143.5 mm Hg, with a mean of 154 mm Hg – was due to the rosuvastatin and half to the antihypertensive therapy. Our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously,” he noted. Dr. Yusuf discussed the findings in a video interview.

The double-blind trial included a diverse population of 12,705 men age 55 or older and women age 65 or older in 21 countries. All were at intermediate cardiovascular risk by conventional stratification methods; none had a history of cardiovascular disease. They were randomized to rosuvastatin or placebo, dual antihypertensive therapy or placebo, or to all three medications or double placebo. The combined-therapy group experienced a 33.7 mg/dL greater drop in LDL-cholesterol and a 6.2 mm Hg bigger reduction in systolic blood pressure than in patients on dual placebo.

During a median followup of 5.6 years, the composite rate of cardiovascular death, nonfatal MI, or nonfatal stroke was 3.6% in the combined-therapy group and 5.0% with dual placebo, for a relative risk reduction of 29%. The number needed to treat for 5.6 years in order to prevent one event of the composite outcome was 72. However, the separation in the event rate curves for the two groups grew larger over time. With an additional planned followup of 3-5 years in HOPE-3, it’s likely the benefits will become even greater, according to Dr. Yusuf.

Combination therapy proved safe. Muscle aches and weakness as well as lightheadedness were more common in the combined treatment group than with dual placebo. However, permanent discontinuation rates were similar in the two groups.

HOPE-3 coinvestigator Dr. Eva Lonn presented the comparison between patients randomized to antihypertensive therapy without rosuvastatin or to placebo. In a prespecified subgroup analysis, active treatment resulted in a significant 27% reduction in the risk of the composite outcome compared with placebo in patients in the top one-third of baseline systolic blood pressure, no benefit in those with a systolic blood pressure of 131.6-143.5 mm Hg, and a suggestion of possible harm in patients whose systolic pressure at enrollment was 131.5 mm Hg or less.

Thus, the study helps define the minimum blood pressure at which antihypertensive therapy becomes beneficial, noted Dr. Lonn, professor of cardiology at McMaster University.

Dr. Yusuf said enthusiasm for the polypill concept as a means of reducing the growing global burden of cardiovascular disease remains strong among many experts. There is broad interest in a polypill for secondary prevention that will include aspirin, a beta blocker, and an ACE inhibitor of angiotensin receptor blocker as a low-cost means of improving medication adherence. And several large clinical trials of the polypill concept for primary prevention are underway, including a randomized trial conducted by Dr. Yusuf and coworkers in which several thousand high-risk subjects without baseline cardiovascular disease will receive a combination of a statin plus not two but three antihypertensive drugs.

Discussant Dr. Donald M. Lloyd-Jones commented, “What strikes me about HOPE-3 is that this is a population at risk, but not at particularly high risk.” And yet these patients benefited from statin therapy regardless of their baseline LDL, noted Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago, and an architect of the risk-based approach to statin use that’s a centerpiece of the current ACC/AHA guidelines on atherosclerotic cardiovascular risk reduction.

In an interview, Dr. Sidney C. Smith, Jr., said the HOPE-3 data are “worthy of consideration” as experts meet at ACC 16 to begin updating guidelines for the treatment of hypertension. In particular, the key findings that moderate-risk hypertensive patients benefited from a statin regardless of their baseline LDL and initiation of blood pressure-lowering therapy was beneficial for patients with a systolic blood pressure in the 140s but not in those with a systolic pressure in the 120s and 130s could be practice changing, according to Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.

Drs. Yusuf and Lonn reported receiving institutional research grants from the Canadian Institutes of Health Research and AstraZeneca, which funded the trial.

Simultaneous with the presentation of the HOPE-3 results at ACC 16 in Chicago, the study on cholesterol lowering and the study on blood pressure and cholesterol lowering led by Dr. Yusef as well as the study on blood pressure lowering led by Dr. Lonn were published online at NEJM.org.

bjancin@frontlinemedcom.com

CHICAGO – The success in the HOPE-3 trial of a two-pronged strategy of a statin plus moderate-dose antihypertensive therapy has expanded the boundaries of primary preventive pharmacotherapy to incorporate many intermediate-cardiovascular-risk patients without cardiovascular disease.

In the Heart Outcomes Evaluation (HOPE)-3 trial, the combination of rosuvastatin (Crestor) at 10 mg/day plus antihypertensive therapy with 16 mg/day of candesartan and 12.5 mg/day of hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL-cholesterol and inflammatory biomarker levels. In nonhypertensive study participants, however, blood pressure-lowering therapy provided no added benefit beyond that achieved with the statin alone, which yielded a 25% relative risk reduction in cardiovascular events compared with placebo, Dr. Salim Yusuf reported at the annual meeting of the American College of Cardiology.

The HOPE-3 trial was the first formal study of the polypill concept of fixed-dose, low-dose combination therapy as a public health tool for primary prevention in an intermediate-risk population without cardiovascular disease. It’s a simple, low-cost, safe, pragmatic preventive strategy that doesn’t require baseline laboratory measurements, dose titration visits, or frequent safety monitoring, he noted.

“The original concept of the polypill was to give it to everyone over age 55. We found in HOPE-3 that the polypill concept is not valid for everybody. It demonstrated benefit in hypertensives but not in nonhypertensives, where a statin alone was beneficial,” said Dr. Yusuf, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“The clinical implication is that statins should be used much more widely than they currently are. Most guidelines for hypertension don’t say to give a statin. But HOPE-3 is saying hypertensives will benefit. About half of the 40% reduction in the risk of cardiovascular events we saw with combination therapy in patients in the highest third for baseline systolic blood pressure – that is, above 143.5 mm Hg, with a mean of 154 mm Hg – was due to the rosuvastatin and half to the antihypertensive therapy. Our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously,” he noted. Dr. Yusuf discussed the findings in a video interview.

The double-blind trial included a diverse population of 12,705 men age 55 or older and women age 65 or older in 21 countries. All were at intermediate cardiovascular risk by conventional stratification methods; none had a history of cardiovascular disease. They were randomized to rosuvastatin or placebo, dual antihypertensive therapy or placebo, or to all three medications or double placebo. The combined-therapy group experienced a 33.7 mg/dL greater drop in LDL-cholesterol and a 6.2 mm Hg bigger reduction in systolic blood pressure than in patients on dual placebo.

During a median followup of 5.6 years, the composite rate of cardiovascular death, nonfatal MI, or nonfatal stroke was 3.6% in the combined-therapy group and 5.0% with dual placebo, for a relative risk reduction of 29%. The number needed to treat for 5.6 years in order to prevent one event of the composite outcome was 72. However, the separation in the event rate curves for the two groups grew larger over time. With an additional planned followup of 3-5 years in HOPE-3, it’s likely the benefits will become even greater, according to Dr. Yusuf.

Combination therapy proved safe. Muscle aches and weakness as well as lightheadedness were more common in the combined treatment group than with dual placebo. However, permanent discontinuation rates were similar in the two groups.

HOPE-3 coinvestigator Dr. Eva Lonn presented the comparison between patients randomized to antihypertensive therapy without rosuvastatin or to placebo. In a prespecified subgroup analysis, active treatment resulted in a significant 27% reduction in the risk of the composite outcome compared with placebo in patients in the top one-third of baseline systolic blood pressure, no benefit in those with a systolic blood pressure of 131.6-143.5 mm Hg, and a suggestion of possible harm in patients whose systolic pressure at enrollment was 131.5 mm Hg or less.

Thus, the study helps define the minimum blood pressure at which antihypertensive therapy becomes beneficial, noted Dr. Lonn, professor of cardiology at McMaster University.

Dr. Yusuf said enthusiasm for the polypill concept as a means of reducing the growing global burden of cardiovascular disease remains strong among many experts. There is broad interest in a polypill for secondary prevention that will include aspirin, a beta blocker, and an ACE inhibitor of angiotensin receptor blocker as a low-cost means of improving medication adherence. And several large clinical trials of the polypill concept for primary prevention are underway, including a randomized trial conducted by Dr. Yusuf and coworkers in which several thousand high-risk subjects without baseline cardiovascular disease will receive a combination of a statin plus not two but three antihypertensive drugs.

Discussant Dr. Donald M. Lloyd-Jones commented, “What strikes me about HOPE-3 is that this is a population at risk, but not at particularly high risk.” And yet these patients benefited from statin therapy regardless of their baseline LDL, noted Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago, and an architect of the risk-based approach to statin use that’s a centerpiece of the current ACC/AHA guidelines on atherosclerotic cardiovascular risk reduction.

In an interview, Dr. Sidney C. Smith, Jr., said the HOPE-3 data are “worthy of consideration” as experts meet at ACC 16 to begin updating guidelines for the treatment of hypertension. In particular, the key findings that moderate-risk hypertensive patients benefited from a statin regardless of their baseline LDL and initiation of blood pressure-lowering therapy was beneficial for patients with a systolic blood pressure in the 140s but not in those with a systolic pressure in the 120s and 130s could be practice changing, according to Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.

Drs. Yusuf and Lonn reported receiving institutional research grants from the Canadian Institutes of Health Research and AstraZeneca, which funded the trial.

Simultaneous with the presentation of the HOPE-3 results at ACC 16 in Chicago, the study on cholesterol lowering and the study on blood pressure and cholesterol lowering led by Dr. Yusef as well as the study on blood pressure lowering led by Dr. Lonn were published online at NEJM.org.

bjancin@frontlinemedcom.com

CHICAGO – The HOPE-3 trial has brought the primary prevention of cardiovascular disease front-and-center as a hot topic of discussion at the annual meeting of the American College of Cardiology.

The large, randomized trial provides new evidence of a significant reduction in cardiovascular events in an intermediate-risk population that hasn’t previously been the focus of risk reduction via pharmacotherapy.

The double-blind study randomized nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease to lipid-lowering with rosuvastatin (Crestor) at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke compared with placebo-treated controls. Impressively, the benefit was similar regardless of baseline LDL-cholesterol level; however, only subjects with hypertension benefited from the dual-antihypertensive therapy.

In this interview, Dr. B. Hadley Wilson of the Sanger Clinic in Charlotte, N.C., explains why he considers HOPE-3 to be a giant step forward in preventive cardiolo

bjancin@frontlinemedcom.com

CHICAGO – The HOPE-3 trial has brought the primary prevention of cardiovascular disease front-and-center as a hot topic of discussion at the annual meeting of the American College of Cardiology.

The large, randomized trial provides new evidence of a significant reduction in cardiovascular events in an intermediate-risk population that hasn’t previously been the focus of risk reduction via pharmacotherapy.

The double-blind study randomized nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease to lipid-lowering with rosuvastatin (Crestor) at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke compared with placebo-treated controls. Impressively, the benefit was similar regardless of baseline LDL-cholesterol level; however, only subjects with hypertension benefited from the dual-antihypertensive therapy.

In this interview, Dr. B. Hadley Wilson of the Sanger Clinic in Charlotte, N.C., explains why he considers HOPE-3 to be a giant step forward in preventive cardiolo

bjancin@frontlinemedcom.com

CHICAGO – The HOPE-3 trial has brought the primary prevention of cardiovascular disease front-and-center as a hot topic of discussion at the annual meeting of the American College of Cardiology.

The large, randomized trial provides new evidence of a significant reduction in cardiovascular events in an intermediate-risk population that hasn’t previously been the focus of risk reduction via pharmacotherapy.

The double-blind study randomized nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease to lipid-lowering with rosuvastatin (Crestor) at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke compared with placebo-treated controls. Impressively, the benefit was similar regardless of baseline LDL-cholesterol level; however, only subjects with hypertension benefited from the dual-antihypertensive therapy.

In this interview, Dr. B. Hadley Wilson of the Sanger Clinic in Charlotte, N.C., explains why he considers HOPE-3 to be a giant step forward in preventive cardiolo

bjancin@frontlinemedcom.com

MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.

“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.

Bruce Jancin/Frontline Medical News

Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.

Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.

“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.

It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.

Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.

Diphenoxylate/atropine (Lomotil) is another effective prescription option.

Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.

The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.

Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”

Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.

Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.

“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.

He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.

bjancin@frontlinemedcom.com

MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.

“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.

Bruce Jancin/Frontline Medical News

Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.

Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.

“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.

It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.

Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.

Diphenoxylate/atropine (Lomotil) is another effective prescription option.

Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.

The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.

Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”

Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.

Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.

“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.

He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.

bjancin@frontlinemedcom.com

MAUI, HAWAII – If you’re going to prescribe apremilast for psoriasis or psoriatic arthritis – and more and more physicians are doing so because of the drug’s exceptional safety profile – you’d better get familiar with the oral phosphodiesterase-4 inhibitor’s gastrointestinal side effects, Dr. George M. Martin advised at the 2016 Rheumatology Winter Clinical Symposium.

“One of the biggest hurdles we have to deal with when we prescribe apremilast is the fact that there are these GI side effects,” said Dr. Martin, a dermatologist practicing in Maui and codirector of the rheumatology symposium.

Bruce Jancin/Frontline Medical News

Celgene, which markets apremilast (Otezla), sponsored an analysis of the pattern of diarrhea that emerged in the pooled results of the phase III ESTEEM 1 and 2 trials of apremilast at 30 mg twice daily for psoriasis and the PALACE 1-3 phase III psoriatic arthritis trials.

Diarrhea occurred in 16%-18% of patients on apremilast, a rate roughly threefold greater than in placebo-treated controls. Diarrhea onset was usually within the first 14 days of therapy. When it occurred, the duration was typically about 2 weeks.

“This you can relay to your patients so they’re not surprised if it happens,” the dermatologist said.

It’s a secretory diarrhea, and it is believed to be a classwide effect for the phosphodiesterase-4 (PDE-4) inhibitors. For example, roflumilast (Daliresp), an oral PDE-4 inhibitor used in the treatment of chronic obstructive pulmonary disease, has the same diarrhea issues. The mechanism has been worked out: The drug increases intracellular cyclic adenosine monophosphate, with resultant activation of chloride channels in crypts in the small bowel, which in turn leads to secretion of chloride ions. It takes the large bowel a couple of weeks to adapt. Caffeine causes diarrhea in some individuals through a similar mechanism.

Apremilast-related diarrhea often responds to the time-tested OTC remedies, including bismuth salicylate or fiber supplements. Alternatively, Dr. Martin said he is a fan of the oral prescription agent crofelemer (Fulyzaq) because of its exceptional safety, tolerability, and effectiveness. Plus, many residents of the garden islands of Hawaii like the idea of using a botanical derived from the latexlike sap – known as ‘dragon’s blood – of a South American tree. Crofelemer’s approved indication is the treatment of diarrhea associated with anti-HIV agents.

Diphenoxylate/atropine (Lomotil) is another effective prescription option.

Nausea and/or vomiting occurred in 15%-17% of apremilast-treated patients in the phase III trials. As with diarrhea, if nausea and/or vomiting is going to happen, it occurs early, within the first week or two. Dr. Martin said he finds in his own practice that the nausea/vomiting is less bothersome for patients than the diarrhea. Drug discontinuation due to any GI side effects is rarely necessary.

The nausea/vomiting is usually readily managed by encouraging affected patients to make sure that they’re well hydrated, take their apremilast with food, and eat smaller, more frequent meals. OTC diphenhydramine (Benadryl) is often effective, as are the usual prescription antiemetic agents.

Pharmaceutical industry data indicate apremilast has quickly captured a 17% share of the market for systemic psoriasis therapies. There is a good reason for that, according to Dr. Martin: “Dermatologists have historically been risk averse. And apremilast is arguably the safest systemic agent we have to treat psoriasis. The beauty of apremilast is it requires no laboratory monitoring. That makes it attractive to dermatologists who are concerned about systemic therapy. It’s why there has been a huge jump in adoption of apremilast.”

Apremilast is comparable to methotrexate in terms of efficacy as reflected in week 16 PASI-75 response rates of about 35%, meaning 35% of treated patients obtain at least a 75% improvement in Psoriasis Area and Severity Index scores, he continued. Apremilast is particularly effective for scalp and nail psoriasis, making it a good option for patients who have psoriasis at those sites but not extensive involvement elsewhere, which might call for the use of a more potent biologic agent.

Surveys indicate that 20% of dermatologists write 80% of all prescriptions for biologic agents used to treat psoriasis. The thinking was that apremilast would appeal to the 80% of dermatologists who have steered clear of the biologics, and that after becoming comfortable with apremilast, they might become more receptive to using biologics for their patients with an inadequate response to the oral PDE-4 inhibitor. That hasn’t happened yet.

“We’re not seeing apremilast function as the gateway drug we thought it would be. It’s just going to take some time for those prescribers either to refer their patients who aren’t getting a good response to the next doctor who’s more adept at treating with biologic agents, or perhaps they themselves will get more involved,” Dr. Martin predicted.

He reported serving on scientific advisory boards for, and/or as a consultant to, nine pharmaceutical companies.

bjancin@frontlinemedcom.com