Bruce Jancin

STOCKHOLM – Levels of four biomarkers appear to predict risk for cardiovascular events in patients with the triad of type 2 diabetes, moderate chronic kidney disease, and anemia, a group for whom most cardiovascular risk factors are not predictive.

In a new secondary analysis of a major randomized clinical trial, urinary protein/creatinine ratio and levels of C-reactive protein, troponin T, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) each provided additional prognostic information and independently predicted cardiovascular outcome in this population of patients, "who, by the way, we’re all seeing more and more in ordinary cardiology practice," Dr. John J.V. McMurray said at the congress.

"The finding that surprised me the most was that 45% of these ambulatory patients with type 2 diabetes and relatively mild anemia and renal dysfunction not requiring dialysis had an elevated troponin T, and 38% had a clearly elevated NT-proBNP," added Dr. McMurray, professor of medical cardiology at the University of Glasgow (Scotland).

In this analysis, NT-proBNP was the single most powerful predictor of outcome. It was an even stronger predictor than advanced age or baseline heart failure. Moreover, cardiac troponin T (TnT), NT-proBNP, C-reactive protein (CRP), and urinary protein/creatinine ratio (UPCR) accounted for four of the top eight predictors of cardiovascular events in patients with the triad of type 2 diabetes, chronic kidney disease, and anemia.

Dr. McMurray presented a secondary, post hoc analysis of data from TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy), an international, double-blind, randomized, placebo-controlled, phase III study involving 4,038 patients with the triad at 623 centers. They were assigned to darbepoetin alfa (Aranesp) or placebo in order to test the hypothesis that raising their hemoglobin level would lessen the rates of death, cardiovascular morbidity, and/or end-stage renal disease during a median 2.4 years of follow-up. It did not.

Indeed, TREAT was a negative study. Darbepoetin alfa therapy not only failed to reduce the primary cardiovascular end point, it doubled the stroke risk, which Dr. McMurray and coinvestigators concluded was not balanced by the modest quality of life benefit and reduced need for RBC transfusion in the active treatment arm (N. Engl. J. Med. 2009;361:2019-32).

In a post hoc analysis of the data, the TREAT investigators found that most of the standard cardiovascular risk factors were nonpredictive in the TREAT triad population. Among these nonpredictive variables were baseline blood pressure, lipid levels, smoking history, body mass index, and a history of peripheral artery disease, lung disease, diabetic complications, and gout. Yet the triad population was clearly at high cardiovascular risk, with roughly a 25% incidence of the composite end point of cardiovascular death, MI, stroke, or hospitalization for heart failure or myocardial ischemia during 2.4 years of follow-up.

The investigators then looked for novel predictors, including biomarkers. The UPCR and CRP markers immediately stood out. In an analysis that was adjusted for other predictive variables, TREAT participants in the bottom tertile for both CRP and UPCR had a 6% annual rate of the composite cardiovascular end point, rising to 20% in those in the highest tertile for both.

Next the investigators turned to NT-proBNP and TnT, which were measured in the first 1,000 subjects. After controlling for other outcome predictors, including UPCR and CRP, the researchers found that the adjusted annual risk of the composite end point in patients who were in the lowest tertile for NT-proBNP and had an undetectable TnT was 5%, climbing stepwise to 30% per year in those in the top tertile for NT-proBNP and a TnT greater than the median 0.028 ng/mL. That’s nearly a sevenfold difference in annualized risk, the cardiologist noted.

"We believe that in addition to aiding risk stratification, these plasma and urinary biomarkers may help in understanding the mechanisms of cardiac risk in this important patient population and suggest new therapeutic strategies in this population," Dr. McMurray concluded.

Discussant Dr. Karl Swedberg recalculated the TREAT data using a different statistical method and came up with a slightly different rank ordering of risk predictors. By his measure, the most powerful predictor of cardiovascular events was baseline CRP, with a chi-squared value of 19.1, followed closely by NT-proBNP, age, TnT, and heart failure. Thus, biomarkers accounted for three of the five strongest predictors, with UPCR lying further down the list, albeit still a significant predictor. But this rearrangement is a small matter, he added.

"I fully concur with the conclusions of Dr. McMurray. I think they’re important, valuable, and will probably be useful," said Dr. Swedberg, professor of medicine at the University of Gothenburg (Sweden).

TREAT was sponsored by Amgen. Dr. McMurray disclosed having received research funding and consulting fees from the company.

STOCKHOLM – Levels of four biomarkers appear to predict risk for cardiovascular events in patients with the triad of type 2 diabetes, moderate chronic kidney disease, and anemia, a group for whom most cardiovascular risk factors are not predictive.

In a new secondary analysis of a major randomized clinical trial, urinary protein/creatinine ratio and levels of C-reactive protein, troponin T, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) each provided additional prognostic information and independently predicted cardiovascular outcome in this population of patients, "who, by the way, we’re all seeing more and more in ordinary cardiology practice," Dr. John J.V. McMurray said at the congress.

"The finding that surprised me the most was that 45% of these ambulatory patients with type 2 diabetes and relatively mild anemia and renal dysfunction not requiring dialysis had an elevated troponin T, and 38% had a clearly elevated NT-proBNP," added Dr. McMurray, professor of medical cardiology at the University of Glasgow (Scotland).

In this analysis, NT-proBNP was the single most powerful predictor of outcome. It was an even stronger predictor than advanced age or baseline heart failure. Moreover, cardiac troponin T (TnT), NT-proBNP, C-reactive protein (CRP), and urinary protein/creatinine ratio (UPCR) accounted for four of the top eight predictors of cardiovascular events in patients with the triad of type 2 diabetes, chronic kidney disease, and anemia.

Dr. McMurray presented a secondary, post hoc analysis of data from TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy), an international, double-blind, randomized, placebo-controlled, phase III study involving 4,038 patients with the triad at 623 centers. They were assigned to darbepoetin alfa (Aranesp) or placebo in order to test the hypothesis that raising their hemoglobin level would lessen the rates of death, cardiovascular morbidity, and/or end-stage renal disease during a median 2.4 years of follow-up. It did not.

Indeed, TREAT was a negative study. Darbepoetin alfa therapy not only failed to reduce the primary cardiovascular end point, it doubled the stroke risk, which Dr. McMurray and coinvestigators concluded was not balanced by the modest quality of life benefit and reduced need for RBC transfusion in the active treatment arm (N. Engl. J. Med. 2009;361:2019-32).

In a post hoc analysis of the data, the TREAT investigators found that most of the standard cardiovascular risk factors were nonpredictive in the TREAT triad population. Among these nonpredictive variables were baseline blood pressure, lipid levels, smoking history, body mass index, and a history of peripheral artery disease, lung disease, diabetic complications, and gout. Yet the triad population was clearly at high cardiovascular risk, with roughly a 25% incidence of the composite end point of cardiovascular death, MI, stroke, or hospitalization for heart failure or myocardial ischemia during 2.4 years of follow-up.

The investigators then looked for novel predictors, including biomarkers. The UPCR and CRP markers immediately stood out. In an analysis that was adjusted for other predictive variables, TREAT participants in the bottom tertile for both CRP and UPCR had a 6% annual rate of the composite cardiovascular end point, rising to 20% in those in the highest tertile for both.

Next the investigators turned to NT-proBNP and TnT, which were measured in the first 1,000 subjects. After controlling for other outcome predictors, including UPCR and CRP, the researchers found that the adjusted annual risk of the composite end point in patients who were in the lowest tertile for NT-proBNP and had an undetectable TnT was 5%, climbing stepwise to 30% per year in those in the top tertile for NT-proBNP and a TnT greater than the median 0.028 ng/mL. That’s nearly a sevenfold difference in annualized risk, the cardiologist noted.

"We believe that in addition to aiding risk stratification, these plasma and urinary biomarkers may help in understanding the mechanisms of cardiac risk in this important patient population and suggest new therapeutic strategies in this population," Dr. McMurray concluded.

Discussant Dr. Karl Swedberg recalculated the TREAT data using a different statistical method and came up with a slightly different rank ordering of risk predictors. By his measure, the most powerful predictor of cardiovascular events was baseline CRP, with a chi-squared value of 19.1, followed closely by NT-proBNP, age, TnT, and heart failure. Thus, biomarkers accounted for three of the five strongest predictors, with UPCR lying further down the list, albeit still a significant predictor. But this rearrangement is a small matter, he added.

"I fully concur with the conclusions of Dr. McMurray. I think they’re important, valuable, and will probably be useful," said Dr. Swedberg, professor of medicine at the University of Gothenburg (Sweden).

TREAT was sponsored by Amgen. Dr. McMurray disclosed having received research funding and consulting fees from the company.

STOCKHOLM – Levels of four biomarkers appear to predict risk for cardiovascular events in patients with the triad of type 2 diabetes, moderate chronic kidney disease, and anemia, a group for whom most cardiovascular risk factors are not predictive.

In a new secondary analysis of a major randomized clinical trial, urinary protein/creatinine ratio and levels of C-reactive protein, troponin T, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) each provided additional prognostic information and independently predicted cardiovascular outcome in this population of patients, "who, by the way, we’re all seeing more and more in ordinary cardiology practice," Dr. John J.V. McMurray said at the congress.

"The finding that surprised me the most was that 45% of these ambulatory patients with type 2 diabetes and relatively mild anemia and renal dysfunction not requiring dialysis had an elevated troponin T, and 38% had a clearly elevated NT-proBNP," added Dr. McMurray, professor of medical cardiology at the University of Glasgow (Scotland).

In this analysis, NT-proBNP was the single most powerful predictor of outcome. It was an even stronger predictor than advanced age or baseline heart failure. Moreover, cardiac troponin T (TnT), NT-proBNP, C-reactive protein (CRP), and urinary protein/creatinine ratio (UPCR) accounted for four of the top eight predictors of cardiovascular events in patients with the triad of type 2 diabetes, chronic kidney disease, and anemia.

Dr. McMurray presented a secondary, post hoc analysis of data from TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy), an international, double-blind, randomized, placebo-controlled, phase III study involving 4,038 patients with the triad at 623 centers. They were assigned to darbepoetin alfa (Aranesp) or placebo in order to test the hypothesis that raising their hemoglobin level would lessen the rates of death, cardiovascular morbidity, and/or end-stage renal disease during a median 2.4 years of follow-up. It did not.

Indeed, TREAT was a negative study. Darbepoetin alfa therapy not only failed to reduce the primary cardiovascular end point, it doubled the stroke risk, which Dr. McMurray and coinvestigators concluded was not balanced by the modest quality of life benefit and reduced need for RBC transfusion in the active treatment arm (N. Engl. J. Med. 2009;361:2019-32).

In a post hoc analysis of the data, the TREAT investigators found that most of the standard cardiovascular risk factors were nonpredictive in the TREAT triad population. Among these nonpredictive variables were baseline blood pressure, lipid levels, smoking history, body mass index, and a history of peripheral artery disease, lung disease, diabetic complications, and gout. Yet the triad population was clearly at high cardiovascular risk, with roughly a 25% incidence of the composite end point of cardiovascular death, MI, stroke, or hospitalization for heart failure or myocardial ischemia during 2.4 years of follow-up.

The investigators then looked for novel predictors, including biomarkers. The UPCR and CRP markers immediately stood out. In an analysis that was adjusted for other predictive variables, TREAT participants in the bottom tertile for both CRP and UPCR had a 6% annual rate of the composite cardiovascular end point, rising to 20% in those in the highest tertile for both.

Next the investigators turned to NT-proBNP and TnT, which were measured in the first 1,000 subjects. After controlling for other outcome predictors, including UPCR and CRP, the researchers found that the adjusted annual risk of the composite end point in patients who were in the lowest tertile for NT-proBNP and had an undetectable TnT was 5%, climbing stepwise to 30% per year in those in the top tertile for NT-proBNP and a TnT greater than the median 0.028 ng/mL. That’s nearly a sevenfold difference in annualized risk, the cardiologist noted.

"We believe that in addition to aiding risk stratification, these plasma and urinary biomarkers may help in understanding the mechanisms of cardiac risk in this important patient population and suggest new therapeutic strategies in this population," Dr. McMurray concluded.

Discussant Dr. Karl Swedberg recalculated the TREAT data using a different statistical method and came up with a slightly different rank ordering of risk predictors. By his measure, the most powerful predictor of cardiovascular events was baseline CRP, with a chi-squared value of 19.1, followed closely by NT-proBNP, age, TnT, and heart failure. Thus, biomarkers accounted for three of the five strongest predictors, with UPCR lying further down the list, albeit still a significant predictor. But this rearrangement is a small matter, he added.

"I fully concur with the conclusions of Dr. McMurray. I think they’re important, valuable, and will probably be useful," said Dr. Swedberg, professor of medicine at the University of Gothenburg (Sweden).

TREAT was sponsored by Amgen. Dr. McMurray disclosed having received research funding and consulting fees from the company.

STOCKHOLM – Levels of four biomarkers appear to predict risk for cardiovascular events in patients with the triad of type 2 diabetes, moderate chronic kidney disease, and anemia, a group for whom most cardiovascular risk factors are not predictive.

In a new secondary analysis of a major randomized clinical trial, urinary protein/creatinine ratio and levels of C-reactive protein, troponin T, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) each provided additional prognostic information and independently predicted cardiovascular outcome in this population of patients, "who, by the way, we’re all seeing more and more in ordinary cardiology practice," Dr. John J.V. McMurray said at the congress.

"The finding that surprised me the most was that 45% of these ambulatory patients with type 2 diabetes and relatively mild anemia and renal dysfunction not requiring dialysis had an elevated troponin T, and 38% had a clearly elevated NT-proBNP," added Dr. McMurray, professor of medical cardiology at the University of Glasgow (Scotland).

In this analysis, NT-proBNP was the single most powerful predictor of outcome. It was an even stronger predictor than advanced age or baseline heart failure. Moreover, cardiac troponin T (TnT), NT-proBNP, C-reactive protein (CRP), and urinary protein/creatinine ratio (UPCR) accounted for four of the top eight predictors of cardiovascular events in patients with the triad of type 2 diabetes, chronic kidney disease, and anemia.

Dr. McMurray presented a secondary, post hoc analysis of data from TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy), an international, double-blind, randomized, placebo-controlled, phase III study involving 4,038 patients with the triad at 623 centers. They were assigned to darbepoetin alfa (Aranesp) or placebo in order to test the hypothesis that raising their hemoglobin level would lessen the rates of death, cardiovascular morbidity, and/or end-stage renal disease during a median 2.4 years of follow-up. It did not.

Indeed, TREAT was a negative study. Darbepoetin alfa therapy not only failed to reduce the primary cardiovascular end point, it doubled the stroke risk, which Dr. McMurray and coinvestigators concluded was not balanced by the modest quality of life benefit and reduced need for RBC transfusion in the active treatment arm (N. Engl. J. Med. 2009;361:2019-32).

In a post hoc analysis of the data, the TREAT investigators found that most of the standard cardiovascular risk factors were nonpredictive in the TREAT triad population. Among these nonpredictive variables were baseline blood pressure, lipid levels, smoking history, body mass index, and a history of peripheral artery disease, lung disease, diabetic complications, and gout. Yet the triad population was clearly at high cardiovascular risk, with roughly a 25% incidence of the composite end point of cardiovascular death, MI, stroke, or hospitalization for heart failure or myocardial ischemia during 2.4 years of follow-up.

The investigators then looked for novel predictors, including biomarkers. The UPCR and CRP markers immediately stood out. In an analysis that was adjusted for other predictive variables, TREAT participants in the bottom tertile for both CRP and UPCR had a 6% annual rate of the composite cardiovascular end point, rising to 20% in those in the highest tertile for both.

Next the investigators turned to NT-proBNP and TnT, which were measured in the first 1,000 subjects. After controlling for other outcome predictors, including UPCR and CRP, the researchers found that the adjusted annual risk of the composite end point in patients who were in the lowest tertile for NT-proBNP and had an undetectable TnT was 5%, climbing stepwise to 30% per year in those in the top tertile for NT-proBNP and a TnT greater than the median 0.028 ng/mL. That’s nearly a sevenfold difference in annualized risk, the cardiologist noted.

"We believe that in addition to aiding risk stratification, these plasma and urinary biomarkers may help in understanding the mechanisms of cardiac risk in this important patient population and suggest new therapeutic strategies in this population," Dr. McMurray concluded.

Discussant Dr. Karl Swedberg recalculated the TREAT data using a different statistical method and came up with a slightly different rank ordering of risk predictors. By his measure, the most powerful predictor of cardiovascular events was baseline CRP, with a chi-squared value of 19.1, followed closely by NT-proBNP, age, TnT, and heart failure. Thus, biomarkers accounted for three of the five strongest predictors, with UPCR lying further down the list, albeit still a significant predictor. But this rearrangement is a small matter, he added.

"I fully concur with the conclusions of Dr. McMurray. I think they’re important, valuable, and will probably be useful," said Dr. Swedberg, professor of medicine at the University of Gothenburg (Sweden).

TREAT was sponsored by Amgen. Dr. McMurray disclosed having received research funding and consulting fees from the company.

STOCKHOLM – Levels of four biomarkers appear to predict risk for cardiovascular events in patients with the triad of type 2 diabetes, moderate chronic kidney disease, and anemia, a group for whom most cardiovascular risk factors are not predictive.

In a new secondary analysis of a major randomized clinical trial, urinary protein/creatinine ratio and levels of C-reactive protein, troponin T, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) each provided additional prognostic information and independently predicted cardiovascular outcome in this population of patients, "who, by the way, we’re all seeing more and more in ordinary cardiology practice," Dr. John J.V. McMurray said at the congress.

"The finding that surprised me the most was that 45% of these ambulatory patients with type 2 diabetes and relatively mild anemia and renal dysfunction not requiring dialysis had an elevated troponin T, and 38% had a clearly elevated NT-proBNP," added Dr. McMurray, professor of medical cardiology at the University of Glasgow (Scotland).

In this analysis, NT-proBNP was the single most powerful predictor of outcome. It was an even stronger predictor than advanced age or baseline heart failure. Moreover, cardiac troponin T (TnT), NT-proBNP, C-reactive protein (CRP), and urinary protein/creatinine ratio (UPCR) accounted for four of the top eight predictors of cardiovascular events in patients with the triad of type 2 diabetes, chronic kidney disease, and anemia.

Dr. McMurray presented a secondary, post hoc analysis of data from TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy), an international, double-blind, randomized, placebo-controlled, phase III study involving 4,038 patients with the triad at 623 centers. They were assigned to darbepoetin alfa (Aranesp) or placebo in order to test the hypothesis that raising their hemoglobin level would lessen the rates of death, cardiovascular morbidity, and/or end-stage renal disease during a median 2.4 years of follow-up. It did not.

Indeed, TREAT was a negative study. Darbepoetin alfa therapy not only failed to reduce the primary cardiovascular end point, it doubled the stroke risk, which Dr. McMurray and coinvestigators concluded was not balanced by the modest quality of life benefit and reduced need for RBC transfusion in the active treatment arm (N. Engl. J. Med. 2009;361:2019-32).

In a post hoc analysis of the data, the TREAT investigators found that most of the standard cardiovascular risk factors were nonpredictive in the TREAT triad population. Among these nonpredictive variables were baseline blood pressure, lipid levels, smoking history, body mass index, and a history of peripheral artery disease, lung disease, diabetic complications, and gout. Yet the triad population was clearly at high cardiovascular risk, with roughly a 25% incidence of the composite end point of cardiovascular death, MI, stroke, or hospitalization for heart failure or myocardial ischemia during 2.4 years of follow-up.

The investigators then looked for novel predictors, including biomarkers. The UPCR and CRP markers immediately stood out. In an analysis that was adjusted for other predictive variables, TREAT participants in the bottom tertile for both CRP and UPCR had a 6% annual rate of the composite cardiovascular end point, rising to 20% in those in the highest tertile for both.

Next the investigators turned to NT-proBNP and TnT, which were measured in the first 1,000 subjects. After controlling for other outcome predictors, including UPCR and CRP, the researchers found that the adjusted annual risk of the composite end point in patients who were in the lowest tertile for NT-proBNP and had an undetectable TnT was 5%, climbing stepwise to 30% per year in those in the top tertile for NT-proBNP and a TnT greater than the median 0.028 ng/mL. That’s nearly a sevenfold difference in annualized risk, the cardiologist noted.

"We believe that in addition to aiding risk stratification, these plasma and urinary biomarkers may help in understanding the mechanisms of cardiac risk in this important patient population and suggest new therapeutic strategies in this population," Dr. McMurray concluded.

Discussant Dr. Karl Swedberg recalculated the TREAT data using a different statistical method and came up with a slightly different rank ordering of risk predictors. By his measure, the most powerful predictor of cardiovascular events was baseline CRP, with a chi-squared value of 19.1, followed closely by NT-proBNP, age, TnT, and heart failure. Thus, biomarkers accounted for three of the five strongest predictors, with UPCR lying further down the list, albeit still a significant predictor. But this rearrangement is a small matter, he added.

"I fully concur with the conclusions of Dr. McMurray. I think they’re important, valuable, and will probably be useful," said Dr. Swedberg, professor of medicine at the University of Gothenburg (Sweden).

TREAT was sponsored by Amgen. Dr. McMurray disclosed having received research funding and consulting fees from the company.

STOCKHOLM – Levels of four biomarkers appear to predict risk for cardiovascular events in patients with the triad of type 2 diabetes, moderate chronic kidney disease, and anemia, a group for whom most cardiovascular risk factors are not predictive.

In a new secondary analysis of a major randomized clinical trial, urinary protein/creatinine ratio and levels of C-reactive protein, troponin T, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) each provided additional prognostic information and independently predicted cardiovascular outcome in this population of patients, "who, by the way, we’re all seeing more and more in ordinary cardiology practice," Dr. John J.V. McMurray said at the congress.

"The finding that surprised me the most was that 45% of these ambulatory patients with type 2 diabetes and relatively mild anemia and renal dysfunction not requiring dialysis had an elevated troponin T, and 38% had a clearly elevated NT-proBNP," added Dr. McMurray, professor of medical cardiology at the University of Glasgow (Scotland).

In this analysis, NT-proBNP was the single most powerful predictor of outcome. It was an even stronger predictor than advanced age or baseline heart failure. Moreover, cardiac troponin T (TnT), NT-proBNP, C-reactive protein (CRP), and urinary protein/creatinine ratio (UPCR) accounted for four of the top eight predictors of cardiovascular events in patients with the triad of type 2 diabetes, chronic kidney disease, and anemia.

Dr. McMurray presented a secondary, post hoc analysis of data from TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy), an international, double-blind, randomized, placebo-controlled, phase III study involving 4,038 patients with the triad at 623 centers. They were assigned to darbepoetin alfa (Aranesp) or placebo in order to test the hypothesis that raising their hemoglobin level would lessen the rates of death, cardiovascular morbidity, and/or end-stage renal disease during a median 2.4 years of follow-up. It did not.

Indeed, TREAT was a negative study. Darbepoetin alfa therapy not only failed to reduce the primary cardiovascular end point, it doubled the stroke risk, which Dr. McMurray and coinvestigators concluded was not balanced by the modest quality of life benefit and reduced need for RBC transfusion in the active treatment arm (N. Engl. J. Med. 2009;361:2019-32).

In a post hoc analysis of the data, the TREAT investigators found that most of the standard cardiovascular risk factors were nonpredictive in the TREAT triad population. Among these nonpredictive variables were baseline blood pressure, lipid levels, smoking history, body mass index, and a history of peripheral artery disease, lung disease, diabetic complications, and gout. Yet the triad population was clearly at high cardiovascular risk, with roughly a 25% incidence of the composite end point of cardiovascular death, MI, stroke, or hospitalization for heart failure or myocardial ischemia during 2.4 years of follow-up.

The investigators then looked for novel predictors, including biomarkers. The UPCR and CRP markers immediately stood out. In an analysis that was adjusted for other predictive variables, TREAT participants in the bottom tertile for both CRP and UPCR had a 6% annual rate of the composite cardiovascular end point, rising to 20% in those in the highest tertile for both.

Next the investigators turned to NT-proBNP and TnT, which were measured in the first 1,000 subjects. After controlling for other outcome predictors, including UPCR and CRP, the researchers found that the adjusted annual risk of the composite end point in patients who were in the lowest tertile for NT-proBNP and had an undetectable TnT was 5%, climbing stepwise to 30% per year in those in the top tertile for NT-proBNP and a TnT greater than the median 0.028 ng/mL. That’s nearly a sevenfold difference in annualized risk, the cardiologist noted.

"We believe that in addition to aiding risk stratification, these plasma and urinary biomarkers may help in understanding the mechanisms of cardiac risk in this important patient population and suggest new therapeutic strategies in this population," Dr. McMurray concluded.

Discussant Dr. Karl Swedberg recalculated the TREAT data using a different statistical method and came up with a slightly different rank ordering of risk predictors. By his measure, the most powerful predictor of cardiovascular events was baseline CRP, with a chi-squared value of 19.1, followed closely by NT-proBNP, age, TnT, and heart failure. Thus, biomarkers accounted for three of the five strongest predictors, with UPCR lying further down the list, albeit still a significant predictor. But this rearrangement is a small matter, he added.

"I fully concur with the conclusions of Dr. McMurray. I think they’re important, valuable, and will probably be useful," said Dr. Swedberg, professor of medicine at the University of Gothenburg (Sweden).

TREAT was sponsored by Amgen. Dr. McMurray disclosed having received research funding and consulting fees from the company.

GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.

"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.

She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.

In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.

Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.

After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.

Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.

Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.

The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.

Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.

Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.

Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.

Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.

GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.

"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.

She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.

In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.

Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.

After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.

Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.

Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.

The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.

Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.

Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.

Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.

Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.

GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.

"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.

She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.

In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.

Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.

After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.

Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.

Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.

The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.

Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.

Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.

Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.

Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.

GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.

"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.

She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.

In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.

Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.

After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.

Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.

Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.

The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.

Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.

Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.

Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.

Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.

GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.

"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.

She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.

In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.

Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.

After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.

Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.

Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.

The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.

Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.

Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.

Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.

Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.

GOTHENBURG, SWEDEN - Oral propranolol proved superior to oral prednisone for treatment of complicated infantile hemangiomas in a retrospective, blinded, matched-pairs comparative study.

"We believe that propranolol should be a first-line therapy for problematic infantile hemangiomas. It brought a more rapid and impressive degree of improvement. And although there were no serious adverse events in either treatment group, the overall safety profile of propranolol was superior," Dr. Janie Bertrand said at the annual congress of the European Academy of Dermatology and Venereology.

She added a caveat, however: This was a small retrospective study. Definitive conclusions regarding propranolol’s place in the treatment of problematic infantile hemangiomas must await the outcome of a large ongoing, international, prospective, randomized clinical trial, said Dr. Bertrand, a dermatology resident at the University of Montreal.

In the interim, the blinded, matched-pairs study moves the field beyond the realm of anecdotal experience. The study involved 12 pairs of infants treated for complicated infantile hemangiomas on the eyelid, cheek, forehead, nose, parotid gland, and/or lip at an academic pediatric tertiary medical center. The infant pairs were matched for age, as well as the location, size, and type of hemangioma. Twelve infants were treated with a mean propranolol dose of 2.7 mg/kg per day starting at a mean age of 3.6 months. The other 12 received oral prednisone at a mean dose of 2.8 mg/kg per day starting at age 3.2 months.

Two blinded evaluators assessed the degree of clinical improvement based on medical photographs taken 1, 2, and 6 months after the start of treatment. They also rated the degree of improvement at 6 months using a 100-mm visual analog scale.

After 1 month, 4 of 12 children on propranolol were rated as showing moderate improvement, meaning a 25%-50% improvement over baseline, while the other 8 showed good improvement, with a 50%-75% gain. In contrast, just one child in the prednisone group showed moderate improvement, seven showed a slight improvement of less than 25%, three were unchanged from baseline, and one was worse.

Results were also significantly better in the propranolol group at 2 and 6 months. After 6 months on propranolol all patients showed good to excellent improvement, whereas the prednisone group showed slight to moderate improvement.

Using the visual analog scale, the evaluators rated the propranolol group as showing a mean 78.7% improvement, compared with baseline, while the prednisone group had a mean 44.8% improvement, Dr. Bertrand said.

The mean treatment duration was 12.7 months in the prednisone arm and 10.6 months with propranolol.

Adverse events in the propranolol group consisted of sleep disturbance in six patients, transient asymptomatic hypotension in one, and vomiting in one. Two patients in the prednisone group experienced oral thrush, one had hypertension, one had growth failure, two displayed irritability, and one developed insomnia.

Clinical improvement was apparent after just a few days on propranolol, probably because of the beta-blocker’s vasoconstrictive effect. Likely mechanisms of clinical benefit include stimulation of apoptosis, downregulation of angiogenic factors, and reduction of skin levels of inflammation-promoting matrix metalloproteinase-9, according to Dr. Bertrand.

Until the results of the ongoing international, randomized trial are in, a baseline cardiac evaluation should be considered mandatory when oral propranolol is being considered for treatment of an infantile hemangioma. The drug should be used with caution in patients at risk for hypoglycemia, as well in those with bronchospastic disease or PHACE syndrome with cerebrovascular anomalies. A prospective study of topical beta-blocker therapy as a means of reducing the risk of systemic side effects is warranted, she added.

Dr. Bertrand declared having no relevant financial interests. The study was conducted with university funding.

GOTHENBURG, SWEDEN - New evidence identifying the optimal dosing regimen for methotrexate in psoriasis comes from a just-completed year-long randomized clinical trial.

"There's a huge long-standing discussion about which is the best dosing regimen for methotrexate. I think we will be able to give you an answer today," promised Dr. Kristian Reich.

That he did, highlighting the oral methotrexate arm of a new phase-III randomized trial of briakinumab, an investigational, fully human monoclonal antibody–targeting interleukin-12 and interleukin-23, in which the biologic agent was compared to oral methotrexate used in a dosing regimen designed to minimize potential toxicities.

The take-home messages regarding methotrexate from the M10-255 study:

• Nearly 60% of psoriasis patients who are started on methotrexate will discontinue the drug during the first year due to lack of efficacy.

• A starting dose of 15 mg once weekly is well tolerated and effective; in only a small percentage of patients is up-titration beneficial.

• Patients who show a good response to methotrexate 15 mg/week by week 6-8 have a high probability of having a full PASI 75 response after 52 weeks.

• Methotrexate’s safety profile in psoriasis patients is better than it’s often painted, based upon the favorable results of the briakinumab study and phase-III trials of two other biologic agents featuring methotrexate arms.

• The peak response to methotrexate is seen by week 16-20 and thereafter declines steadily.

"I think that for many dermatologists there was a perception that the longer we give methotrexate, the better this drug is going to be. Wrong!" declared Dr. Reich, professor of dermatology at the University of Göttingen, Germany.

Confirmation on this score comes from the methotrexate arm of the phase-III Raptiva (efalizumab) Evaluation of Safety and Treatment Optimization (RESTORE) study. The highest PASI 75 response rate to methotrexate in RESTORE was seen at week 16, when patients were on 15 or 20 mg/week. This was followed by a nearly 12% absolute decline in PASI 75 responders between weeks 16 and 26, he added at the satellite symposium supported by Abbott.

"I think these studies may change the way we view methotrexate," Dr. Reich observed.

The M10-255 trial involved 317 psoriasis patients with a mean baseline PASI score of 18 and a 19-year history of the disease. They were randomized to briakinumab or to oral methotrexate with folic acid on the following schedule: 5 mg of methotrexate on week 1, 10 mg during week 2, 15 mg/week for weeks 3-9, and then an increase to 20 mg/week if a PASI 75 wasn’t achieved on week 10. If a PASI 75 was not reached by week 16, the weekly dose could be further increased to 25 mg.

Of the patients in the methotrexate arm, 72% had discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate due to adverse events.

A PASI 75 efficacy end point was achieved in 40% of patients in the methotrexate arm at 24 weeks and in 24% at week 52.

"In only a low percentage of patients was the week-10 increase to 20 mg/week necessary and helpful to make them achieve a PASI 75 response. And there is no evidence that the further increase to 25 mg is doing any good to the patient," Dr. Reich reported.

This 40% PASI 75 response at week 24 is quite similar to what was seen earlier in the methotrexate arms of the RESTORE and Comparative Study of Humira vs. Methotrexate vs. Placebo in Psoriasis Patients (CHAMPION) trials, which recorded week-16 PASI 75s of 36% and 42%, respectively.

"These three trials used three different methotrexate dosing regimens. Let’s get this straight: The methotrexate efficacy was independent of the dosing regimens. No matter if you started with a low dose of 5 mg or with 15 mg straight away, the efficacy was the same. The safety profile of methotrexate was also very similar across these trials," the dermatologist continued.

Dr. Reich said these three trials have changed the way he approaches methotrexate therapy in psoriasis.

"I will no longer use the Weinstein regimen or start with a 5-mg test dose. I think it’s fair to say, based on these data, that we can start with 15 mg right away. However, it is now for me absolutely clear that methotrexate is going to produce a good response in 35%-40% of patients, and that’s it. And it’s not true that the longer we give methotrexate the higher the clinical response will be. We are going to see a decrease, as with every psoriasis drug, beyond week 16-20," according to Dr. Reich.

He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott, which funded the M10-255 trial, as well as Biogen Idec, Bristol-Myers-Squibb, Centocor, Merck Serono, Schering-Plough, UCB Pharma, and Wyeth.

GOTHENBURG, SWEDEN - New evidence identifying the optimal dosing regimen for methotrexate in psoriasis comes from a just-completed year-long randomized clinical trial.

"There's a huge long-standing discussion about which is the best dosing regimen for methotrexate. I think we will be able to give you an answer today," promised Dr. Kristian Reich.

That he did, highlighting the oral methotrexate arm of a new phase-III randomized trial of briakinumab, an investigational, fully human monoclonal antibody–targeting interleukin-12 and interleukin-23, in which the biologic agent was compared to oral methotrexate used in a dosing regimen designed to minimize potential toxicities.

The take-home messages regarding methotrexate from the M10-255 study:

• Nearly 60% of psoriasis patients who are started on methotrexate will discontinue the drug during the first year due to lack of efficacy.

• A starting dose of 15 mg once weekly is well tolerated and effective; in only a small percentage of patients is up-titration beneficial.

• Patients who show a good response to methotrexate 15 mg/week by week 6-8 have a high probability of having a full PASI 75 response after 52 weeks.

• Methotrexate’s safety profile in psoriasis patients is better than it’s often painted, based upon the favorable results of the briakinumab study and phase-III trials of two other biologic agents featuring methotrexate arms.

• The peak response to methotrexate is seen by week 16-20 and thereafter declines steadily.

"I think that for many dermatologists there was a perception that the longer we give methotrexate, the better this drug is going to be. Wrong!" declared Dr. Reich, professor of dermatology at the University of Göttingen, Germany.

Confirmation on this score comes from the methotrexate arm of the phase-III Raptiva (efalizumab) Evaluation of Safety and Treatment Optimization (RESTORE) study. The highest PASI 75 response rate to methotrexate in RESTORE was seen at week 16, when patients were on 15 or 20 mg/week. This was followed by a nearly 12% absolute decline in PASI 75 responders between weeks 16 and 26, he added at the satellite symposium supported by Abbott.

"I think these studies may change the way we view methotrexate," Dr. Reich observed.

The M10-255 trial involved 317 psoriasis patients with a mean baseline PASI score of 18 and a 19-year history of the disease. They were randomized to briakinumab or to oral methotrexate with folic acid on the following schedule: 5 mg of methotrexate on week 1, 10 mg during week 2, 15 mg/week for weeks 3-9, and then an increase to 20 mg/week if a PASI 75 wasn’t achieved on week 10. If a PASI 75 was not reached by week 16, the weekly dose could be further increased to 25 mg.

Of the patients in the methotrexate arm, 72% had discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate due to adverse events.

A PASI 75 efficacy end point was achieved in 40% of patients in the methotrexate arm at 24 weeks and in 24% at week 52.

"In only a low percentage of patients was the week-10 increase to 20 mg/week necessary and helpful to make them achieve a PASI 75 response. And there is no evidence that the further increase to 25 mg is doing any good to the patient," Dr. Reich reported.

This 40% PASI 75 response at week 24 is quite similar to what was seen earlier in the methotrexate arms of the RESTORE and Comparative Study of Humira vs. Methotrexate vs. Placebo in Psoriasis Patients (CHAMPION) trials, which recorded week-16 PASI 75s of 36% and 42%, respectively.

"These three trials used three different methotrexate dosing regimens. Let’s get this straight: The methotrexate efficacy was independent of the dosing regimens. No matter if you started with a low dose of 5 mg or with 15 mg straight away, the efficacy was the same. The safety profile of methotrexate was also very similar across these trials," the dermatologist continued.

Dr. Reich said these three trials have changed the way he approaches methotrexate therapy in psoriasis.

"I will no longer use the Weinstein regimen or start with a 5-mg test dose. I think it’s fair to say, based on these data, that we can start with 15 mg right away. However, it is now for me absolutely clear that methotrexate is going to produce a good response in 35%-40% of patients, and that’s it. And it’s not true that the longer we give methotrexate the higher the clinical response will be. We are going to see a decrease, as with every psoriasis drug, beyond week 16-20," according to Dr. Reich.

He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott, which funded the M10-255 trial, as well as Biogen Idec, Bristol-Myers-Squibb, Centocor, Merck Serono, Schering-Plough, UCB Pharma, and Wyeth.

GOTHENBURG, SWEDEN - New evidence identifying the optimal dosing regimen for methotrexate in psoriasis comes from a just-completed year-long randomized clinical trial.

"There's a huge long-standing discussion about which is the best dosing regimen for methotrexate. I think we will be able to give you an answer today," promised Dr. Kristian Reich.

That he did, highlighting the oral methotrexate arm of a new phase-III randomized trial of briakinumab, an investigational, fully human monoclonal antibody–targeting interleukin-12 and interleukin-23, in which the biologic agent was compared to oral methotrexate used in a dosing regimen designed to minimize potential toxicities.

The take-home messages regarding methotrexate from the M10-255 study:

• Nearly 60% of psoriasis patients who are started on methotrexate will discontinue the drug during the first year due to lack of efficacy.

• A starting dose of 15 mg once weekly is well tolerated and effective; in only a small percentage of patients is up-titration beneficial.

• Patients who show a good response to methotrexate 15 mg/week by week 6-8 have a high probability of having a full PASI 75 response after 52 weeks.

• Methotrexate’s safety profile in psoriasis patients is better than it’s often painted, based upon the favorable results of the briakinumab study and phase-III trials of two other biologic agents featuring methotrexate arms.

• The peak response to methotrexate is seen by week 16-20 and thereafter declines steadily.

"I think that for many dermatologists there was a perception that the longer we give methotrexate, the better this drug is going to be. Wrong!" declared Dr. Reich, professor of dermatology at the University of Göttingen, Germany.

Confirmation on this score comes from the methotrexate arm of the phase-III Raptiva (efalizumab) Evaluation of Safety and Treatment Optimization (RESTORE) study. The highest PASI 75 response rate to methotrexate in RESTORE was seen at week 16, when patients were on 15 or 20 mg/week. This was followed by a nearly 12% absolute decline in PASI 75 responders between weeks 16 and 26, he added at the satellite symposium supported by Abbott.

"I think these studies may change the way we view methotrexate," Dr. Reich observed.

The M10-255 trial involved 317 psoriasis patients with a mean baseline PASI score of 18 and a 19-year history of the disease. They were randomized to briakinumab or to oral methotrexate with folic acid on the following schedule: 5 mg of methotrexate on week 1, 10 mg during week 2, 15 mg/week for weeks 3-9, and then an increase to 20 mg/week if a PASI 75 wasn’t achieved on week 10. If a PASI 75 was not reached by week 16, the weekly dose could be further increased to 25 mg.

Of the patients in the methotrexate arm, 72% had discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate due to adverse events.

A PASI 75 efficacy end point was achieved in 40% of patients in the methotrexate arm at 24 weeks and in 24% at week 52.

"In only a low percentage of patients was the week-10 increase to 20 mg/week necessary and helpful to make them achieve a PASI 75 response. And there is no evidence that the further increase to 25 mg is doing any good to the patient," Dr. Reich reported.

This 40% PASI 75 response at week 24 is quite similar to what was seen earlier in the methotrexate arms of the RESTORE and Comparative Study of Humira vs. Methotrexate vs. Placebo in Psoriasis Patients (CHAMPION) trials, which recorded week-16 PASI 75s of 36% and 42%, respectively.

"These three trials used three different methotrexate dosing regimens. Let’s get this straight: The methotrexate efficacy was independent of the dosing regimens. No matter if you started with a low dose of 5 mg or with 15 mg straight away, the efficacy was the same. The safety profile of methotrexate was also very similar across these trials," the dermatologist continued.

Dr. Reich said these three trials have changed the way he approaches methotrexate therapy in psoriasis.

"I will no longer use the Weinstein regimen or start with a 5-mg test dose. I think it’s fair to say, based on these data, that we can start with 15 mg right away. However, it is now for me absolutely clear that methotrexate is going to produce a good response in 35%-40% of patients, and that’s it. And it’s not true that the longer we give methotrexate the higher the clinical response will be. We are going to see a decrease, as with every psoriasis drug, beyond week 16-20," according to Dr. Reich.

He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott, which funded the M10-255 trial, as well as Biogen Idec, Bristol-Myers-Squibb, Centocor, Merck Serono, Schering-Plough, UCB Pharma, and Wyeth.

GOTHENBURG, SWEDEN - New evidence identifying the optimal dosing regimen for methotrexate in psoriasis comes from a just-completed year-long randomized clinical trial.

"There's a huge long-standing discussion about which is the best dosing regimen for methotrexate. I think we will be able to give you an answer today," promised Dr. Kristian Reich.

That he did, highlighting the oral methotrexate arm of a new phase-III randomized trial of briakinumab, an investigational, fully human monoclonal antibody–targeting interleukin-12 and interleukin-23, in which the biologic agent was compared to oral methotrexate used in a dosing regimen designed to minimize potential toxicities.

The take-home messages regarding methotrexate from the M10-255 study:

• Nearly 60% of psoriasis patients who are started on methotrexate will discontinue the drug during the first year due to lack of efficacy.

• A starting dose of 15 mg once weekly is well tolerated and effective; in only a small percentage of patients is up-titration beneficial.

• Patients who show a good response to methotrexate 15 mg/week by week 6-8 have a high probability of having a full PASI 75 response after 52 weeks.

• Methotrexate’s safety profile in psoriasis patients is better than it’s often painted, based upon the favorable results of the briakinumab study and phase-III trials of two other biologic agents featuring methotrexate arms.

• The peak response to methotrexate is seen by week 16-20 and thereafter declines steadily.

"I think that for many dermatologists there was a perception that the longer we give methotrexate, the better this drug is going to be. Wrong!" declared Dr. Reich, professor of dermatology at the University of Göttingen, Germany.

Confirmation on this score comes from the methotrexate arm of the phase-III Raptiva (efalizumab) Evaluation of Safety and Treatment Optimization (RESTORE) study. The highest PASI 75 response rate to methotrexate in RESTORE was seen at week 16, when patients were on 15 or 20 mg/week. This was followed by a nearly 12% absolute decline in PASI 75 responders between weeks 16 and 26, he added at the satellite symposium supported by Abbott.

"I think these studies may change the way we view methotrexate," Dr. Reich observed.

The M10-255 trial involved 317 psoriasis patients with a mean baseline PASI score of 18 and a 19-year history of the disease. They were randomized to briakinumab or to oral methotrexate with folic acid on the following schedule: 5 mg of methotrexate on week 1, 10 mg during week 2, 15 mg/week for weeks 3-9, and then an increase to 20 mg/week if a PASI 75 wasn’t achieved on week 10. If a PASI 75 was not reached by week 16, the weekly dose could be further increased to 25 mg.

Of the patients in the methotrexate arm, 72% had discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate due to adverse events.

A PASI 75 efficacy end point was achieved in 40% of patients in the methotrexate arm at 24 weeks and in 24% at week 52.

"In only a low percentage of patients was the week-10 increase to 20 mg/week necessary and helpful to make them achieve a PASI 75 response. And there is no evidence that the further increase to 25 mg is doing any good to the patient," Dr. Reich reported.

This 40% PASI 75 response at week 24 is quite similar to what was seen earlier in the methotrexate arms of the RESTORE and Comparative Study of Humira vs. Methotrexate vs. Placebo in Psoriasis Patients (CHAMPION) trials, which recorded week-16 PASI 75s of 36% and 42%, respectively.

"These three trials used three different methotrexate dosing regimens. Let's get this straight: The methotrexate efficacy was independent of the dosing regimens. No matter if you started with a low dose of 5 mg or with 15 mg straight away, the efficacy was the same. The safety profile of methotrexate was also very similar across these trials," the dermatologist continued.

Dr. Reich said these three trials have changed the way he approaches methotrexate therapy in psoriasis.

"I will no longer use the Weinstein regimen or start with a 5-mg test dose. I think it's fair to say, based on these data, that we can start with 15 mg right away. However, it is now for me absolutely clear that methotrexate is going to produce a good response in 35%-40% of patients, and that's it. And it's not true that the longer we give methotrexate the higher the clinical response will be. We are going to see a decrease, as with every psoriasis drug, beyond week 16-20," according to Dr. Reich.

He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott, which funded the M10-255 trial, as well as Biogen Idec, Bristol-Myers-Squibb, Centocor, Merck Serono, Schering-Plough, UCB Pharma, and Wyeth.

GOTHENBURG, SWEDEN - New evidence identifying the optimal dosing regimen for methotrexate in psoriasis comes from a just-completed year-long randomized clinical trial.

"There's a huge long-standing discussion about which is the best dosing regimen for methotrexate. I think we will be able to give you an answer today," promised Dr. Kristian Reich.

That he did, highlighting the oral methotrexate arm of a new phase-III randomized trial of briakinumab, an investigational, fully human monoclonal antibody–targeting interleukin-12 and interleukin-23, in which the biologic agent was compared to oral methotrexate used in a dosing regimen designed to minimize potential toxicities.

The take-home messages regarding methotrexate from the M10-255 study:

• Nearly 60% of psoriasis patients who are started on methotrexate will discontinue the drug during the first year due to lack of efficacy.

• A starting dose of 15 mg once weekly is well tolerated and effective; in only a small percentage of patients is up-titration beneficial.

• Patients who show a good response to methotrexate 15 mg/week by week 6-8 have a high probability of having a full PASI 75 response after 52 weeks.

• Methotrexate’s safety profile in psoriasis patients is better than it’s often painted, based upon the favorable results of the briakinumab study and phase-III trials of two other biologic agents featuring methotrexate arms.

• The peak response to methotrexate is seen by week 16-20 and thereafter declines steadily.

"I think that for many dermatologists there was a perception that the longer we give methotrexate, the better this drug is going to be. Wrong!" declared Dr. Reich, professor of dermatology at the University of Göttingen, Germany.

Confirmation on this score comes from the methotrexate arm of the phase-III Raptiva (efalizumab) Evaluation of Safety and Treatment Optimization (RESTORE) study. The highest PASI 75 response rate to methotrexate in RESTORE was seen at week 16, when patients were on 15 or 20 mg/week. This was followed by a nearly 12% absolute decline in PASI 75 responders between weeks 16 and 26, he added at the satellite symposium supported by Abbott.

"I think these studies may change the way we view methotrexate," Dr. Reich observed.

The M10-255 trial involved 317 psoriasis patients with a mean baseline PASI score of 18 and a 19-year history of the disease. They were randomized to briakinumab or to oral methotrexate with folic acid on the following schedule: 5 mg of methotrexate on week 1, 10 mg during week 2, 15 mg/week for weeks 3-9, and then an increase to 20 mg/week if a PASI 75 wasn’t achieved on week 10. If a PASI 75 was not reached by week 16, the weekly dose could be further increased to 25 mg.

Of the patients in the methotrexate arm, 72% had discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate due to adverse events.

A PASI 75 efficacy end point was achieved in 40% of patients in the methotrexate arm at 24 weeks and in 24% at week 52.

"In only a low percentage of patients was the week-10 increase to 20 mg/week necessary and helpful to make them achieve a PASI 75 response. And there is no evidence that the further increase to 25 mg is doing any good to the patient," Dr. Reich reported.

This 40% PASI 75 response at week 24 is quite similar to what was seen earlier in the methotrexate arms of the RESTORE and Comparative Study of Humira vs. Methotrexate vs. Placebo in Psoriasis Patients (CHAMPION) trials, which recorded week-16 PASI 75s of 36% and 42%, respectively.

"These three trials used three different methotrexate dosing regimens. Let's get this straight: The methotrexate efficacy was independent of the dosing regimens. No matter if you started with a low dose of 5 mg or with 15 mg straight away, the efficacy was the same. The safety profile of methotrexate was also very similar across these trials," the dermatologist continued.

Dr. Reich said these three trials have changed the way he approaches methotrexate therapy in psoriasis.

"I will no longer use the Weinstein regimen or start with a 5-mg test dose. I think it's fair to say, based on these data, that we can start with 15 mg right away. However, it is now for me absolutely clear that methotrexate is going to produce a good response in 35%-40% of patients, and that's it. And it's not true that the longer we give methotrexate the higher the clinical response will be. We are going to see a decrease, as with every psoriasis drug, beyond week 16-20," according to Dr. Reich.

He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott, which funded the M10-255 trial, as well as Biogen Idec, Bristol-Myers-Squibb, Centocor, Merck Serono, Schering-Plough, UCB Pharma, and Wyeth.

GOTHENBURG, SWEDEN - New evidence identifying the optimal dosing regimen for methotrexate in psoriasis comes from a just-completed year-long randomized clinical trial.

"There's a huge long-standing discussion about which is the best dosing regimen for methotrexate. I think we will be able to give you an answer today," promised Dr. Kristian Reich.

That he did, highlighting the oral methotrexate arm of a new phase-III randomized trial of briakinumab, an investigational, fully human monoclonal antibody–targeting interleukin-12 and interleukin-23, in which the biologic agent was compared to oral methotrexate used in a dosing regimen designed to minimize potential toxicities.

The take-home messages regarding methotrexate from the M10-255 study:

• Nearly 60% of psoriasis patients who are started on methotrexate will discontinue the drug during the first year due to lack of efficacy.

• A starting dose of 15 mg once weekly is well tolerated and effective; in only a small percentage of patients is up-titration beneficial.

• Patients who show a good response to methotrexate 15 mg/week by week 6-8 have a high probability of having a full PASI 75 response after 52 weeks.

• Methotrexate’s safety profile in psoriasis patients is better than it’s often painted, based upon the favorable results of the briakinumab study and phase-III trials of two other biologic agents featuring methotrexate arms.

• The peak response to methotrexate is seen by week 16-20 and thereafter declines steadily.

"I think that for many dermatologists there was a perception that the longer we give methotrexate, the better this drug is going to be. Wrong!" declared Dr. Reich, professor of dermatology at the University of Göttingen, Germany.

Confirmation on this score comes from the methotrexate arm of the phase-III Raptiva (efalizumab) Evaluation of Safety and Treatment Optimization (RESTORE) study. The highest PASI 75 response rate to methotrexate in RESTORE was seen at week 16, when patients were on 15 or 20 mg/week. This was followed by a nearly 12% absolute decline in PASI 75 responders between weeks 16 and 26, he added at the satellite symposium supported by Abbott.

"I think these studies may change the way we view methotrexate," Dr. Reich observed.

The M10-255 trial involved 317 psoriasis patients with a mean baseline PASI score of 18 and a 19-year history of the disease. They were randomized to briakinumab or to oral methotrexate with folic acid on the following schedule: 5 mg of methotrexate on week 1, 10 mg during week 2, 15 mg/week for weeks 3-9, and then an increase to 20 mg/week if a PASI 75 wasn’t achieved on week 10. If a PASI 75 was not reached by week 16, the weekly dose could be further increased to 25 mg.

Of the patients in the methotrexate arm, 72% had discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate due to adverse events.

A PASI 75 efficacy end point was achieved in 40% of patients in the methotrexate arm at 24 weeks and in 24% at week 52.

"In only a low percentage of patients was the week-10 increase to 20 mg/week necessary and helpful to make them achieve a PASI 75 response. And there is no evidence that the further increase to 25 mg is doing any good to the patient," Dr. Reich reported.

This 40% PASI 75 response at week 24 is quite similar to what was seen earlier in the methotrexate arms of the RESTORE and Comparative Study of Humira vs. Methotrexate vs. Placebo in Psoriasis Patients (CHAMPION) trials, which recorded week-16 PASI 75s of 36% and 42%, respectively.

"These three trials used three different methotrexate dosing regimens. Let's get this straight: The methotrexate efficacy was independent of the dosing regimens. No matter if you started with a low dose of 5 mg or with 15 mg straight away, the efficacy was the same. The safety profile of methotrexate was also very similar across these trials," the dermatologist continued.

Dr. Reich said these three trials have changed the way he approaches methotrexate therapy in psoriasis.

"I will no longer use the Weinstein regimen or start with a 5-mg test dose. I think it's fair to say, based on these data, that we can start with 15 mg right away. However, it is now for me absolutely clear that methotrexate is going to produce a good response in 35%-40% of patients, and that's it. And it's not true that the longer we give methotrexate the higher the clinical response will be. We are going to see a decrease, as with every psoriasis drug, beyond week 16-20," according to Dr. Reich.

He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott, which funded the M10-255 trial, as well as Biogen Idec, Bristol-Myers-Squibb, Centocor, Merck Serono, Schering-Plough, UCB Pharma, and Wyeth.

GOTHENBURG, SWEDEN - Neisseria gonorrhoeae strains are showing a worrisome drift in susceptibility to cephalosporins, causing experts to warn that the bacterium is only a step away from acquiring high-level resistance that would render ineffective the current first-line antimicrobials.

That development could have disastrous consequences since cephalosporins are the last remaining class of antimicrobial agents that are highly effective against N. gonorrhoeae.

"The challenge is to maintain gonorrhea as a treatable infection," Dr. Catherine Ison declared at the annual congress of the European Academy of Dermatology and Venereology.

Because Neisseria gonorrhoeae is highly versatile, that task won’t be easy. The bacterium has a solid track record of acquiring and developing resistance. Since sulfonamide was introduced for the treatment of gonorrhea in the 1930s, N. gonorrhoeae has developed up different mechanisms for evading each new first-line antimicrobial agent. Penicillins, tetracyclines, quinolones, and azithromycin have all fallen by the wayside.

"We should never underestimate the gonococcus. We’ve known that. Those of us who’ve spent our lives working with it know that it always comes up with surprises," observed Dr. Ison, director of the sexually transmitted bacteria reference laboratory at the U.K. Health Protection Agency, London.

The case of ciprofloxacin is a good example of how quickly and relentlessly high-level resistance can occur—and how slow national and international infectious disease treatment guideline panels often are to respond, she remarked.

Ciprofloxacin was recommended as a highly effective first-line agent for gonorrhea beginning in about 1990. However, by 2004, when the European Gonococcal Antimicrobial Surveillance Program (Euro-GASP) was initiated, the mean resistance to ciprofloxacin among N. gonorrhoeae isolates from 17 participating countries was already at 31%. In 2006 it rose to 42%, climbing further to 53% in 2007 and 63% in 2009.

To put these resistance figures into context, the World Health Organization recommends considering switching to a different first-line agent when the prevalence of resistant organisms reaches 5% in order to maintain therapeutic success rates in excess of 95%. By the middle of the past decade resistance rates in Europe exceeded that standard by 8- to 10-fold. Yet European gonorrhea treatment guidelines finally got around to recommending replacement of ciprofloxacin by cephalosporins as first-line agents only a few months ago, Dr. Ison noted.

Resistance to the oral cephalosporin cefixime (Suprax) now stands at an average of about 5% across Europe. Monitoring by Euro-GASP, now funded by the European Center for Disease Prevention and Control, indicates five European countries—Austria, Italy, Denmark, Belgium, and Slovenia—already have rates in excess of 5%. Gonorrhea treatment failures with cefixime have been reported. The mechanism is attributed to penA mosaic. The microorganism will need to acquire additional mechanisms in order for full resistance to occur, but that’s just a matter of time, she said.

As for ceftriaxone (Rocephin), an injectable first-line cephalosporin, the Euro-GASP data for 2004-2009 show a drift in minimum inhibitory concentrations toward the more resistant end of the spectrum over time. There have been occasional reports of treatment failures. The resistance mechanism appears to differ from that for cefixime.

How does this resistance on the part of N. gonorrhoeae happen? The culprits are misuse or overuse of antimicrobials due to an inadequate or incomplete course, the over-the-counter availability existing in some countries, and long-term use of a single agent.

In order to maintain the effectiveness of cefixime and ceftriaxone as long as possible, it’s going to be necessary to think outside the box, Dr. Ison stressed.

"We’re already testing new agents, and retesting old agents as well. We’ve started testing gentamicin as a possibility, for example," she said. "And we’re going to have to think about increasing the dose and using multiple dosing—that’s obviously not something STI physicians want to do, but it may be something they’ll have to do. We may also have to instigate enhanced surveillance of targeted high-risk groups where we lower the threshold for changing therapy."

The Centers for Disease Control and Prevention is already moving in this direction with its recommendation that in selected high-risk groups the cutoff for changing therapy should be lowered from the 5% suggested by the WHO to 3%, she noted.

Meanwhile, Dr. Ison has been involved in helping WHO develop an action plan for resistant gonorrhea outbreak control.

"If we put all of these things together and we act quickly, then we hopefully can retain gonorrhea as a treatable infection," Dr. Ison concluded.

Disclosures: She declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Neisseria gonorrhoeae strains are showing a worrisome drift in susceptibility to cephalosporins, causing experts to warn that the bacterium is only a step away from acquiring high-level resistance that would render ineffective the current first-line antimicrobials.

That development could have disastrous consequences since cephalosporins are the last remaining class of antimicrobial agents that are highly effective against N. gonorrhoeae.

"The challenge is to maintain gonorrhea as a treatable infection," Dr. Catherine Ison declared at the annual congress of the European Academy of Dermatology and Venereology.

Because Neisseria gonorrhoeae is highly versatile, that task won’t be easy. The bacterium has a solid track record of acquiring and developing resistance. Since sulfonamide was introduced for the treatment of gonorrhea in the 1930s, N. gonorrhoeae has developed up different mechanisms for evading each new first-line antimicrobial agent. Penicillins, tetracyclines, quinolones, and azithromycin have all fallen by the wayside.

"We should never underestimate the gonococcus. We’ve known that. Those of us who’ve spent our lives working with it know that it always comes up with surprises," observed Dr. Ison, director of the sexually transmitted bacteria reference laboratory at the U.K. Health Protection Agency, London.

The case of ciprofloxacin is a good example of how quickly and relentlessly high-level resistance can occur—and how slow national and international infectious disease treatment guideline panels often are to respond, she remarked.

Ciprofloxacin was recommended as a highly effective first-line agent for gonorrhea beginning in about 1990. However, by 2004, when the European Gonococcal Antimicrobial Surveillance Program (Euro-GASP) was initiated, the mean resistance to ciprofloxacin among N. gonorrhoeae isolates from 17 participating countries was already at 31%. In 2006 it rose to 42%, climbing further to 53% in 2007 and 63% in 2009.

To put these resistance figures into context, the World Health Organization recommends considering switching to a different first-line agent when the prevalence of resistant organisms reaches 5% in order to maintain therapeutic success rates in excess of 95%. By the middle of the past decade resistance rates in Europe exceeded that standard by 8- to 10-fold. Yet European gonorrhea treatment guidelines finally got around to recommending replacement of ciprofloxacin by cephalosporins as first-line agents only a few months ago, Dr. Ison noted.

Resistance to the oral cephalosporin cefixime (Suprax) now stands at an average of about 5% across Europe. Monitoring by Euro-GASP, now funded by the European Center for Disease Prevention and Control, indicates five European countries—Austria, Italy, Denmark, Belgium, and Slovenia—already have rates in excess of 5%. Gonorrhea treatment failures with cefixime have been reported. The mechanism is attributed to penA mosaic. The microorganism will need to acquire additional mechanisms in order for full resistance to occur, but that’s just a matter of time, she said.

As for ceftriaxone (Rocephin), an injectable first-line cephalosporin, the Euro-GASP data for 2004-2009 show a drift in minimum inhibitory concentrations toward the more resistant end of the spectrum over time. There have been occasional reports of treatment failures. The resistance mechanism appears to differ from that for cefixime.

How does this resistance on the part of N. gonorrhoeae happen? The culprits are misuse or overuse of antimicrobials due to an inadequate or incomplete course, the over-the-counter availability existing in some countries, and long-term use of a single agent.

In order to maintain the effectiveness of cefixime and ceftriaxone as long as possible, it’s going to be necessary to think outside the box, Dr. Ison stressed.

"We’re already testing new agents, and retesting old agents as well. We’ve started testing gentamicin as a possibility, for example," she said. "And we’re going to have to think about increasing the dose and using multiple dosing—that’s obviously not something STI physicians want to do, but it may be something they’ll have to do. We may also have to instigate enhanced surveillance of targeted high-risk groups where we lower the threshold for changing therapy."

The Centers for Disease Control and Prevention is already moving in this direction with its recommendation that in selected high-risk groups the cutoff for changing therapy should be lowered from the 5% suggested by the WHO to 3%, she noted.

Meanwhile, Dr. Ison has been involved in helping WHO develop an action plan for resistant gonorrhea outbreak control.

"If we put all of these things together and we act quickly, then we hopefully can retain gonorrhea as a treatable infection," Dr. Ison concluded.

Disclosures: She declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Neisseria gonorrhoeae strains are showing a worrisome drift in susceptibility to cephalosporins, causing experts to warn that the bacterium is only a step away from acquiring high-level resistance that would render ineffective the current first-line antimicrobials.

That development could have disastrous consequences since cephalosporins are the last remaining class of antimicrobial agents that are highly effective against N. gonorrhoeae.

"The challenge is to maintain gonorrhea as a treatable infection," Dr. Catherine Ison declared at the annual congress of the European Academy of Dermatology and Venereology.

Because Neisseria gonorrhoeae is highly versatile, that task won’t be easy. The bacterium has a solid track record of acquiring and developing resistance. Since sulfonamide was introduced for the treatment of gonorrhea in the 1930s, N. gonorrhoeae has developed up different mechanisms for evading each new first-line antimicrobial agent. Penicillins, tetracyclines, quinolones, and azithromycin have all fallen by the wayside.

"We should never underestimate the gonococcus. We’ve known that. Those of us who’ve spent our lives working with it know that it always comes up with surprises," observed Dr. Ison, director of the sexually transmitted bacteria reference laboratory at the U.K. Health Protection Agency, London.

The case of ciprofloxacin is a good example of how quickly and relentlessly high-level resistance can occur—and how slow national and international infectious disease treatment guideline panels often are to respond, she remarked.

Ciprofloxacin was recommended as a highly effective first-line agent for gonorrhea beginning in about 1990. However, by 2004, when the European Gonococcal Antimicrobial Surveillance Program (Euro-GASP) was initiated, the mean resistance to ciprofloxacin among N. gonorrhoeae isolates from 17 participating countries was already at 31%. In 2006 it rose to 42%, climbing further to 53% in 2007 and 63% in 2009.

To put these resistance figures into context, the World Health Organization recommends considering switching to a different first-line agent when the prevalence of resistant organisms reaches 5% in order to maintain therapeutic success rates in excess of 95%. By the middle of the past decade resistance rates in Europe exceeded that standard by 8- to 10-fold. Yet European gonorrhea treatment guidelines finally got around to recommending replacement of ciprofloxacin by cephalosporins as first-line agents only a few months ago, Dr. Ison noted.

Resistance to the oral cephalosporin cefixime (Suprax) now stands at an average of about 5% across Europe. Monitoring by Euro-GASP, now funded by the European Center for Disease Prevention and Control, indicates five European countries—Austria, Italy, Denmark, Belgium, and Slovenia—already have rates in excess of 5%. Gonorrhea treatment failures with cefixime have been reported. The mechanism is attributed to penA mosaic. The microorganism will need to acquire additional mechanisms in order for full resistance to occur, but that’s just a matter of time, she said.

As for ceftriaxone (Rocephin), an injectable first-line cephalosporin, the Euro-GASP data for 2004-2009 show a drift in minimum inhibitory concentrations toward the more resistant end of the spectrum over time. There have been occasional reports of treatment failures. The resistance mechanism appears to differ from that for cefixime.

How does this resistance on the part of N. gonorrhoeae happen? The culprits are misuse or overuse of antimicrobials due to an inadequate or incomplete course, the over-the-counter availability existing in some countries, and long-term use of a single agent.

In order to maintain the effectiveness of cefixime and ceftriaxone as long as possible, it’s going to be necessary to think outside the box, Dr. Ison stressed.

"We’re already testing new agents, and retesting old agents as well. We’ve started testing gentamicin as a possibility, for example," she said. "And we’re going to have to think about increasing the dose and using multiple dosing—that’s obviously not something STI physicians want to do, but it may be something they’ll have to do. We may also have to instigate enhanced surveillance of targeted high-risk groups where we lower the threshold for changing therapy."

The Centers for Disease Control and Prevention is already moving in this direction with its recommendation that in selected high-risk groups the cutoff for changing therapy should be lowered from the 5% suggested by the WHO to 3%, she noted.

Meanwhile, Dr. Ison has been involved in helping WHO develop an action plan for resistant gonorrhea outbreak control.

"If we put all of these things together and we act quickly, then we hopefully can retain gonorrhea as a treatable infection," Dr. Ison concluded.

Disclosures: She declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Neisseria gonorrhoeae strains are showing a worrisome drift in susceptibility to cephalosporins, causing experts to warn that the bacterium is only a step away from acquiring high-level resistance that would render ineffective the current first-line antimicrobials.

That development could have disastrous consequences since cephalosporins are the last remaining class of antimicrobial agents that are highly effective against N. gonorrhoeae.

"The challenge is to maintain gonorrhea as a treatable infection," Dr. Catherine Ison declared at the annual congress of the European Academy of Dermatology and Venereology.

Because Neisseria gonorrhoeae is highly versatile, that task won’t be easy. The bacterium has a solid track record of acquiring and developing resistance. Since sulfonamide was introduced for the treatment of gonorrhea in the 1930s, N. gonorrhoeae has developed up different mechanisms for evading each new first-line antimicrobial agent. Penicillins, tetracyclines, quinolones, and azithromycin have all fallen by the wayside.

"We should never underestimate the gonococcus. We’ve known that. Those of us who’ve spent our lives working with it know that it always comes up with surprises," observed Dr. Ison, director of the sexually transmitted bacteria reference laboratory at the U.K. Health Protection Agency, London.

The case of ciprofloxacin is a good example of how quickly and relentlessly high-level resistance can occur—and how slow national and international infectious disease treatment guideline panels often are to respond, she remarked.

Ciprofloxacin was recommended as a highly effective first-line agent for gonorrhea beginning in about 1990. However, by 2004, when the European Gonococcal Antimicrobial Surveillance Program (Euro-GASP) was initiated, the mean resistance to ciprofloxacin among N. gonorrhoeae isolates from 17 participating countries was already at 31%. In 2006 it rose to 42%, climbing further to 53% in 2007 and 63% in 2009.

To put these resistance figures into context, the World Health Organization recommends considering switching to a different first-line agent when the prevalence of resistant organisms reaches 5% in order to maintain therapeutic success rates in excess of 95%. By the middle of the past decade resistance rates in Europe exceeded that standard by 8- to 10-fold. Yet European gonorrhea treatment guidelines finally got around to recommending replacement of ciprofloxacin by cephalosporins as first-line agents only a few months ago, Dr. Ison noted.

Resistance to the oral cephalosporin cefixime (Suprax) now stands at an average of about 5% across Europe. Monitoring by Euro-GASP, now funded by the European Center for Disease Prevention and Control, indicates five European countries—Austria, Italy, Denmark, Belgium, and Slovenia—already have rates in excess of 5%. Gonorrhea treatment failures with cefixime have been reported. The mechanism is attributed to penA mosaic. The microorganism will need to acquire additional mechanisms in order for full resistance to occur, but that’s just a matter of time, she said.

As for ceftriaxone (Rocephin), an injectable first-line cephalosporin, the Euro-GASP data for 2004-2009 show a drift in minimum inhibitory concentrations toward the more resistant end of the spectrum over time. There have been occasional reports of treatment failures. The resistance mechanism appears to differ from that for cefixime.

How does this resistance on the part of N. gonorrhoeae happen? The culprits are misuse or overuse of antimicrobials due to an inadequate or incomplete course, the over-the-counter availability existing in some countries, and long-term use of a single agent.

In order to maintain the effectiveness of cefixime and ceftriaxone as long as possible, it’s going to be necessary to think outside the box, Dr. Ison stressed.

"We’re already testing new agents, and retesting old agents as well. We’ve started testing gentamicin as a possibility, for example," she said. "And we’re going to have to think about increasing the dose and using multiple dosing—that’s obviously not something STI physicians want to do, but it may be something they’ll have to do. We may also have to instigate enhanced surveillance of targeted high-risk groups where we lower the threshold for changing therapy."

The Centers for Disease Control and Prevention is already moving in this direction with its recommendation that in selected high-risk groups the cutoff for changing therapy should be lowered from the 5% suggested by the WHO to 3%, she noted.

Meanwhile, Dr. Ison has been involved in helping WHO develop an action plan for resistant gonorrhea outbreak control.

"If we put all of these things together and we act quickly, then we hopefully can retain gonorrhea as a treatable infection," Dr. Ison concluded.

She declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Neisseria gonorrhoeae strains are showing a worrisome drift in susceptibility to cephalosporins, causing experts to warn that the bacterium is only a step away from acquiring high-level resistance that would render ineffective the current first-line antimicrobials.

That development could have disastrous consequences since cephalosporins are the last remaining class of antimicrobial agents that are highly effective against N. gonorrhoeae.

"The challenge is to maintain gonorrhea as a treatable infection," Dr. Catherine Ison declared at the annual congress of the European Academy of Dermatology and Venereology.

Because Neisseria gonorrhoeae is highly versatile, that task won’t be easy. The bacterium has a solid track record of acquiring and developing resistance. Since sulfonamide was introduced for the treatment of gonorrhea in the 1930s, N. gonorrhoeae has developed up different mechanisms for evading each new first-line antimicrobial agent. Penicillins, tetracyclines, quinolones, and azithromycin have all fallen by the wayside.

"We should never underestimate the gonococcus. We’ve known that. Those of us who’ve spent our lives working with it know that it always comes up with surprises," observed Dr. Ison, director of the sexually transmitted bacteria reference laboratory at the U.K. Health Protection Agency, London.

The case of ciprofloxacin is a good example of how quickly and relentlessly high-level resistance can occur—and how slow national and international infectious disease treatment guideline panels often are to respond, she remarked.

Ciprofloxacin was recommended as a highly effective first-line agent for gonorrhea beginning in about 1990. However, by 2004, when the European Gonococcal Antimicrobial Surveillance Program (Euro-GASP) was initiated, the mean resistance to ciprofloxacin among N. gonorrhoeae isolates from 17 participating countries was already at 31%. In 2006 it rose to 42%, climbing further to 53% in 2007 and 63% in 2009.

To put these resistance figures into context, the World Health Organization recommends considering switching to a different first-line agent when the prevalence of resistant organisms reaches 5% in order to maintain therapeutic success rates in excess of 95%. By the middle of the past decade resistance rates in Europe exceeded that standard by 8- to 10-fold. Yet European gonorrhea treatment guidelines finally got around to recommending replacement of ciprofloxacin by cephalosporins as first-line agents only a few months ago, Dr. Ison noted.

Resistance to the oral cephalosporin cefixime (Suprax) now stands at an average of about 5% across Europe. Monitoring by Euro-GASP, now funded by the European Center for Disease Prevention and Control, indicates five European countries—Austria, Italy, Denmark, Belgium, and Slovenia—already have rates in excess of 5%. Gonorrhea treatment failures with cefixime have been reported. The mechanism is attributed to penA mosaic. The microorganism will need to acquire additional mechanisms in order for full resistance to occur, but that’s just a matter of time, she said.

As for ceftriaxone (Rocephin), an injectable first-line cephalosporin, the Euro-GASP data for 2004-2009 show a drift in minimum inhibitory concentrations toward the more resistant end of the spectrum over time. There have been occasional reports of treatment failures. The resistance mechanism appears to differ from that for cefixime.

How does this resistance on the part of N. gonorrhoeae happen? The culprits are misuse or overuse of antimicrobials due to an inadequate or incomplete course, the over-the-counter availability existing in some countries, and long-term use of a single agent.

In order to maintain the effectiveness of cefixime and ceftriaxone as long as possible, it’s going to be necessary to think outside the box, Dr. Ison stressed.

"We’re already testing new agents, and retesting old agents as well. We’ve started testing gentamicin as a possibility, for example," she said. "And we’re going to have to think about increasing the dose and using multiple dosing—that’s obviously not something STI physicians want to do, but it may be something they’ll have to do. We may also have to instigate enhanced surveillance of targeted high-risk groups where we lower the threshold for changing therapy."

The Centers for Disease Control and Prevention is already moving in this direction with its recommendation that in selected high-risk groups the cutoff for changing therapy should be lowered from the 5% suggested by the WHO to 3%, she noted.

Meanwhile, Dr. Ison has been involved in helping WHO develop an action plan for resistant gonorrhea outbreak control.

"If we put all of these things together and we act quickly, then we hopefully can retain gonorrhea as a treatable infection," Dr. Ison concluded.

She declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Neisseria gonorrhoeae strains are showing a worrisome drift in susceptibility to cephalosporins, causing experts to warn that the bacterium is only a step away from acquiring high-level resistance that would render ineffective the current first-line antimicrobials.

That development could have disastrous consequences since cephalosporins are the last remaining class of antimicrobial agents that are highly effective against N. gonorrhoeae.

"The challenge is to maintain gonorrhea as a treatable infection," Dr. Catherine Ison declared at the annual congress of the European Academy of Dermatology and Venereology.

Because Neisseria gonorrhoeae is highly versatile, that task won’t be easy. The bacterium has a solid track record of acquiring and developing resistance. Since sulfonamide was introduced for the treatment of gonorrhea in the 1930s, N. gonorrhoeae has developed up different mechanisms for evading each new first-line antimicrobial agent. Penicillins, tetracyclines, quinolones, and azithromycin have all fallen by the wayside.

"We should never underestimate the gonococcus. We’ve known that. Those of us who’ve spent our lives working with it know that it always comes up with surprises," observed Dr. Ison, director of the sexually transmitted bacteria reference laboratory at the U.K. Health Protection Agency, London.

The case of ciprofloxacin is a good example of how quickly and relentlessly high-level resistance can occur—and how slow national and international infectious disease treatment guideline panels often are to respond, she remarked.

Ciprofloxacin was recommended as a highly effective first-line agent for gonorrhea beginning in about 1990. However, by 2004, when the European Gonococcal Antimicrobial Surveillance Program (Euro-GASP) was initiated, the mean resistance to ciprofloxacin among N. gonorrhoeae isolates from 17 participating countries was already at 31%. In 2006 it rose to 42%, climbing further to 53% in 2007 and 63% in 2009.

To put these resistance figures into context, the World Health Organization recommends considering switching to a different first-line agent when the prevalence of resistant organisms reaches 5% in order to maintain therapeutic success rates in excess of 95%. By the middle of the past decade resistance rates in Europe exceeded that standard by 8- to 10-fold. Yet European gonorrhea treatment guidelines finally got around to recommending replacement of ciprofloxacin by cephalosporins as first-line agents only a few months ago, Dr. Ison noted.

Resistance to the oral cephalosporin cefixime (Suprax) now stands at an average of about 5% across Europe. Monitoring by Euro-GASP, now funded by the European Center for Disease Prevention and Control, indicates five European countries—Austria, Italy, Denmark, Belgium, and Slovenia—already have rates in excess of 5%. Gonorrhea treatment failures with cefixime have been reported. The mechanism is attributed to penA mosaic. The microorganism will need to acquire additional mechanisms in order for full resistance to occur, but that’s just a matter of time, she said.

As for ceftriaxone (Rocephin), an injectable first-line cephalosporin, the Euro-GASP data for 2004-2009 show a drift in minimum inhibitory concentrations toward the more resistant end of the spectrum over time. There have been occasional reports of treatment failures. The resistance mechanism appears to differ from that for cefixime.

How does this resistance on the part of N. gonorrhoeae happen? The culprits are misuse or overuse of antimicrobials due to an inadequate or incomplete course, the over-the-counter availability existing in some countries, and long-term use of a single agent.

In order to maintain the effectiveness of cefixime and ceftriaxone as long as possible, it’s going to be necessary to think outside the box, Dr. Ison stressed.

"We’re already testing new agents, and retesting old agents as well. We’ve started testing gentamicin as a possibility, for example," she said. "And we’re going to have to think about increasing the dose and using multiple dosing—that’s obviously not something STI physicians want to do, but it may be something they’ll have to do. We may also have to instigate enhanced surveillance of targeted high-risk groups where we lower the threshold for changing therapy."

The Centers for Disease Control and Prevention is already moving in this direction with its recommendation that in selected high-risk groups the cutoff for changing therapy should be lowered from the 5% suggested by the WHO to 3%, she noted.

Meanwhile, Dr. Ison has been involved in helping WHO develop an action plan for resistant gonorrhea outbreak control.

"If we put all of these things together and we act quickly, then we hopefully can retain gonorrhea as a treatable infection," Dr. Ison concluded.

She declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Neurofibromatosis type 1 is a diagnosis every dermatologist should be able to make, according to Dr. Sirkku Peltonen.

Be sure to check the armpits, she said. Examining the axillae in search of a few small freckles often makes the difference between diagnosing neurofibromatosis type 1 (NF1) and overlooking this cancer predisposition syndrome.

"The armpits are so easy to forget – and then you lose the chance to make the diagnosis," said Dr. Peltonen of the University of Turku (Finland).

Diagnosis of NF1 is not difficult, she said. Of children aged 6 years or older, 95% can be clinically diagnosed based on the presence of at least two of the following features: six or more café au lait spots, each more than 5 mm in their greatest diameter; axillary or inguinal freckling; a first-degree relative with NF1; or pseudoarthrosis of the tibia, a finding present in only about 3% of individuals with NF1. These four features, from a longer list of diagnostic criteria established by the National Institutes of Health, are the most relevant to dermatologists (JAMA 1997;278:51-7). The flat, pigmented café au lait macules usually appear by a child’s first birthday.

"If you see four or five café au lait spots, suspect NF1 and look for more," Dr. Peltonen said at the annual congress of the European Academy of Dermatology and Venereology.

Freckles under the armpit appear by 6 years of age. Prior to that, the diagnosis is typically made on the basis of the requisite café au lait spots in a child having a family history of NF1. However, half of patients with NF1 have a sporadic mutation and no family history of the disease, making early diagnosis considerably more difficult.

Laboratory analysis of NF1 is available in challenging cases, most of which involve young children. It is a laborious, expensive process because the NF1 gene, located on chromosome 17, band q11, is large, and hundreds of mutations have been identified to date, said Dr. Peltonen.

In her experience, laboratories vary widely in their ability to perform a high-quality analysis of mutations of the NF1 gene. She singled out the laboratories at the Ghent (Belgium) University and the University of Alabama at Birmingham as being particularly good when it comes to the diagnosis of NF1. Testing costs more than $1,300, she said.

The incidence of NF1, formerly known as von Recklinghausen’s disease, is roughly 1 in 3,000 live births, noted Dr. Peltonen. Inheritance is autosomal dominant with 100% penetrance. This means everyone who has the inherited form of NF1 ought to be readily diagnosable.

NF1 is a multisystem condition. Common features include cognitive impairment in 80% of patients, learning difficulties in 50%-60%, and speech abnormalities in 30%, as well as eye and skeletal abnormalities. Affected children are at risk for social exclusion because of their appearance. A dermatologist who diagnoses NF1 needs to be ready to make a referral to a physician who is familiar with the syndrome for regular follow-up, she said.

Children with NF1 are at 100-fold increased risk for brain tumors, compared with unaffected children. The lifetime risk of developing a malignant peripheral nerve sheath tumor is 10%-15%. Thirty percent or more of patients with NF1 have one or more plexiform neuromas, which are at risk for malignant transformation. The cancers can appear at any age, although most often not until after the teenage years.

Danger signs of malignancy in patients with NF1 include neurogenic pain in the extremities, a painful mass, or accelerated growth of an existing plexiform neuroma, she added.

The majority of adults with NF1 develop cutaneous neurofibromas. These were traditionally thought to have their origin in small dermal nerve twigs containing Schwann cells. In soon-to-be-published work, however, Dr. Peltonen and his coworkers have shown that the tumors actually arise from multipotent stem cells closely associated with hair follicles.

The cutaneous neurofibromas never become malignant. Nevertheless, they have a huge negative impact on quality of life, she said.

Patients consider cutaneous neurofibromas to be the greatest burden of NF1 because they are painful and unsightly. Dermatologists can do patients a great service by removing the benign cutaneous tumors, said Dr. Peltonen. The CO2 laser is effective for this purpose. Dozens of tumors can be removed under local anesthesia in one appointment, and patients are very appreciative. Dr. Peltonen has one patient who travels 9 hours each way for excision of cutaneous neurofibromas.

"I usually make a circle around the tumor and then cut in between dermis and the tumor while pulling on it at the same time," she said. "It’s quite easy to get the tumor out of the skin, and the holes heal nicely."

Numerous cancer drugs have been studied and found wanting for the treatment of plexiform neuromas and/or malignant peripheral nerve sheath tumors. Among the agents that have failed are sirolimus, sorafenib, erlotinib, sunitinib, ranibizumab, and cediranib. Imatinib has shown mixed results for the treatment of plexiform neuromas; a clinical trial is ongoing.

Disclosures: Dr. Peltonen said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN - Neurofibromatosis type 1 is a diagnosis every dermatologist should be able to make, according to Dr. Sirkku Peltonen.

Be sure to check the armpits, she said. Examining the axillae in search of a few small freckles often makes the difference between diagnosing neurofibromatosis type 1 (NF1) and overlooking this cancer predisposition syndrome.

"The armpits are so easy to forget – and then you lose the chance to make the diagnosis," said Dr. Peltonen of the University of Turku (Finland).

Diagnosis of NF1 is not difficult, she said. Of children aged 6 years or older, 95% can be clinically diagnosed based on the presence of at least two of the following features: six or more café au lait spots, each more than 5 mm in their greatest diameter; axillary or inguinal freckling; a first-degree relative with NF1; or pseudoarthrosis of the tibia, a finding present in only about 3% of individuals with NF1. These four features, from a longer list of diagnostic criteria established by the National Institutes of Health, are the most relevant to dermatologists (JAMA 1997;278:51-7). The flat, pigmented café au lait macules usually appear by a child’s first birthday.

"If you see four or five café au lait spots, suspect NF1 and look for more," Dr. Peltonen said at the annual congress of the European Academy of Dermatology and Venereology.

Freckles under the armpit appear by 6 years of age. Prior to that, the diagnosis is typically made on the basis of the requisite café au lait spots in a child having a family history of NF1. However, half of patients with NF1 have a sporadic mutation and no family history of the disease, making early diagnosis considerably more difficult.

Laboratory analysis of NF1 is available in challenging cases, most of which involve young children. It is a laborious, expensive process because the NF1 gene, located on chromosome 17, band q11, is large, and hundreds of mutations have been identified to date, said Dr. Peltonen.

In her experience, laboratories vary widely in their ability to perform a high-quality analysis of mutations of the NF1 gene. She singled out the laboratories at the Ghent (Belgium) University and the University of Alabama at Birmingham as being particularly good when it comes to the diagnosis of NF1. Testing costs more than $1,300, she said.

The incidence of NF1, formerly known as von Recklinghausen’s disease, is roughly 1 in 3,000 live births, noted Dr. Peltonen. Inheritance is autosomal dominant with 100% penetrance. This means everyone who has the inherited form of NF1 ought to be readily diagnosable.

NF1 is a multisystem condition. Common features include cognitive impairment in 80% of patients, learning difficulties in 50%-60%, and speech abnormalities in 30%, as well as eye and skeletal abnormalities. Affected children are at risk for social exclusion because of their appearance. A dermatologist who diagnoses NF1 needs to be ready to make a referral to a physician who is familiar with the syndrome for regular follow-up, she said.

Children with NF1 are at 100-fold increased risk for brain tumors, compared with unaffected children. The lifetime risk of developing a malignant peripheral nerve sheath tumor is 10%-15%. Thirty percent or more of patients with NF1 have one or more plexiform neuromas, which are at risk for malignant transformation. The cancers can appear at any age, although most often not until after the teenage years.

Danger signs of malignancy in patients with NF1 include neurogenic pain in the extremities, a painful mass, or accelerated growth of an existing plexiform neuroma, she added.

The majority of adults with NF1 develop cutaneous neurofibromas. These were traditionally thought to have their origin in small dermal nerve twigs containing Schwann cells. In soon-to-be-published work, however, Dr. Peltonen and his coworkers have shown that the tumors actually arise from multipotent stem cells closely associated with hair follicles.

The cutaneous neurofibromas never become malignant. Nevertheless, they have a huge negative impact on quality of life, she said.

Patients consider cutaneous neurofibromas to be the greatest burden of NF1 because they are painful and unsightly. Dermatologists can do patients a great service by removing the benign cutaneous tumors, said Dr. Peltonen. The CO2 laser is effective for this purpose. Dozens of tumors can be removed under local anesthesia in one appointment, and patients are very appreciative. Dr. Peltonen has one patient who travels 9 hours each way for excision of cutaneous neurofibromas.

"I usually make a circle around the tumor and then cut in between dermis and the tumor while pulling on it at the same time," she said. "It’s quite easy to get the tumor out of the skin, and the holes heal nicely."

Numerous cancer drugs have been studied and found wanting for the treatment of plexiform neuromas and/or malignant peripheral nerve sheath tumors. Among the agents that have failed are sirolimus, sorafenib, erlotinib, sunitinib, ranibizumab, and cediranib. Imatinib has shown mixed results for the treatment of plexiform neuromas; a clinical trial is ongoing.

Disclosures: Dr. Peltonen said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN - Neurofibromatosis type 1 is a diagnosis every dermatologist should be able to make, according to Dr. Sirkku Peltonen.

Be sure to check the armpits, she said. Examining the axillae in search of a few small freckles often makes the difference between diagnosing neurofibromatosis type 1 (NF1) and overlooking this cancer predisposition syndrome.

"The armpits are so easy to forget – and then you lose the chance to make the diagnosis," said Dr. Peltonen of the University of Turku (Finland).

Diagnosis of NF1 is not difficult, she said. Of children aged 6 years or older, 95% can be clinically diagnosed based on the presence of at least two of the following features: six or more café au lait spots, each more than 5 mm in their greatest diameter; axillary or inguinal freckling; a first-degree relative with NF1; or pseudoarthrosis of the tibia, a finding present in only about 3% of individuals with NF1. These four features, from a longer list of diagnostic criteria established by the National Institutes of Health, are the most relevant to dermatologists (JAMA 1997;278:51-7). The flat, pigmented café au lait macules usually appear by a child’s first birthday.

"If you see four or five café au lait spots, suspect NF1 and look for more," Dr. Peltonen said at the annual congress of the European Academy of Dermatology and Venereology.

Freckles under the armpit appear by 6 years of age. Prior to that, the diagnosis is typically made on the basis of the requisite café au lait spots in a child having a family history of NF1. However, half of patients with NF1 have a sporadic mutation and no family history of the disease, making early diagnosis considerably more difficult.

Laboratory analysis of NF1 is available in challenging cases, most of which involve young children. It is a laborious, expensive process because the NF1 gene, located on chromosome 17, band q11, is large, and hundreds of mutations have been identified to date, said Dr. Peltonen.

In her experience, laboratories vary widely in their ability to perform a high-quality analysis of mutations of the NF1 gene. She singled out the laboratories at the Ghent (Belgium) University and the University of Alabama at Birmingham as being particularly good when it comes to the diagnosis of NF1. Testing costs more than $1,300, she said.

The incidence of NF1, formerly known as von Recklinghausen’s disease, is roughly 1 in 3,000 live births, noted Dr. Peltonen. Inheritance is autosomal dominant with 100% penetrance. This means everyone who has the inherited form of NF1 ought to be readily diagnosable.

NF1 is a multisystem condition. Common features include cognitive impairment in 80% of patients, learning difficulties in 50%-60%, and speech abnormalities in 30%, as well as eye and skeletal abnormalities. Affected children are at risk for social exclusion because of their appearance. A dermatologist who diagnoses NF1 needs to be ready to make a referral to a physician who is familiar with the syndrome for regular follow-up, she said.

Children with NF1 are at 100-fold increased risk for brain tumors, compared with unaffected children. The lifetime risk of developing a malignant peripheral nerve sheath tumor is 10%-15%. Thirty percent or more of patients with NF1 have one or more plexiform neuromas, which are at risk for malignant transformation. The cancers can appear at any age, although most often not until after the teenage years.

Danger signs of malignancy in patients with NF1 include neurogenic pain in the extremities, a painful mass, or accelerated growth of an existing plexiform neuroma, she added.

The majority of adults with NF1 develop cutaneous neurofibromas. These were traditionally thought to have their origin in small dermal nerve twigs containing Schwann cells. In soon-to-be-published work, however, Dr. Peltonen and his coworkers have shown that the tumors actually arise from multipotent stem cells closely associated with hair follicles.

The cutaneous neurofibromas never become malignant. Nevertheless, they have a huge negative impact on quality of life, she said.

Patients consider cutaneous neurofibromas to be the greatest burden of NF1 because they are painful and unsightly. Dermatologists can do patients a great service by removing the benign cutaneous tumors, said Dr. Peltonen. The CO2 laser is effective for this purpose. Dozens of tumors can be removed under local anesthesia in one appointment, and patients are very appreciative. Dr. Peltonen has one patient who travels 9 hours each way for excision of cutaneous neurofibromas.

"I usually make a circle around the tumor and then cut in between dermis and the tumor while pulling on it at the same time," she said. "It’s quite easy to get the tumor out of the skin, and the holes heal nicely."

Numerous cancer drugs have been studied and found wanting for the treatment of plexiform neuromas and/or malignant peripheral nerve sheath tumors. Among the agents that have failed are sirolimus, sorafenib, erlotinib, sunitinib, ranibizumab, and cediranib. Imatinib has shown mixed results for the treatment of plexiform neuromas; a clinical trial is ongoing.

Disclosures: Dr. Peltonen said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN - Neurofibromatosis type 1 is a diagnosis every dermatologist should be able to make, according to Dr. Sirkku Peltonen.

Be sure to check the armpits, she said. Examining the axillae in search of a few small freckles often makes the difference between diagnosing neurofibromatosis type 1 (NF1) and overlooking this cancer predisposition syndrome.

"The armpits are so easy to forget – and then you lose the chance to make the diagnosis," said Dr. Peltonen of the University of Turku (Finland).

Diagnosis of NF1 is not difficult, she said. Of children aged 6 years or older, 95% can be clinically diagnosed based on the presence of at least two of the following features: six or more café au lait spots, each more than 5 mm in their greatest diameter; axillary or inguinal freckling; a first-degree relative with NF1; or pseudoarthrosis of the tibia, a finding present in only about 3% of individuals with NF1. These four features, from a longer list of diagnostic criteria established by the National Institutes of Health, are the most relevant to dermatologists (JAMA 1997;278:51-7). The flat, pigmented café au lait macules usually appear by a child’s first birthday.

"If you see four or five café au lait spots, suspect NF1 and look for more," Dr. Peltonen said at the annual congress of the European Academy of Dermatology and Venereology.

Freckles under the armpit appear by 6 years of age. Prior to that, the diagnosis is typically made on the basis of the requisite café au lait spots in a child having a family history of NF1. However, half of patients with NF1 have a sporadic mutation and no family history of the disease, making early diagnosis considerably more difficult.

Laboratory analysis of NF1 is available in challenging cases, most of which involve young children. It is a laborious, expensive process because the NF1 gene, located on chromosome 17, band q11, is large, and hundreds of mutations have been identified to date, said Dr. Peltonen.

In her experience, laboratories vary widely in their ability to perform a high-quality analysis of mutations of the NF1 gene. She singled out the laboratories at the Ghent (Belgium) University and the University of Alabama at Birmingham as being particularly good when it comes to the diagnosis of NF1. Testing costs more than $1,300, she said.

The incidence of NF1, formerly known as von Recklinghausen’s disease, is roughly 1 in 3,000 live births, noted Dr. Peltonen. Inheritance is autosomal dominant with 100% penetrance. This means everyone who has the inherited form of NF1 ought to be readily diagnosable.

NF1 is a multisystem condition. Common features include cognitive impairment in 80% of patients, learning difficulties in 50%-60%, and speech abnormalities in 30%, as well as eye and skeletal abnormalities. Affected children are at risk for social exclusion because of their appearance. A dermatologist who diagnoses NF1 needs to be ready to make a referral to a physician who is familiar with the syndrome for regular follow-up, she said.

Children with NF1 are at 100-fold increased risk for brain tumors, compared with unaffected children. The lifetime risk of developing a malignant peripheral nerve sheath tumor is 10%-15%. Thirty percent or more of patients with NF1 have one or more plexiform neuromas, which are at risk for malignant transformation. The cancers can appear at any age, although most often not until after the teenage years.

Danger signs of malignancy in patients with NF1 include neurogenic pain in the extremities, a painful mass, or accelerated growth of an existing plexiform neuroma, she added.

The majority of adults with NF1 develop cutaneous neurofibromas. These were traditionally thought to have their origin in small dermal nerve twigs containing Schwann cells. In soon-to-be-published work, however, Dr. Peltonen and his coworkers have shown that the tumors actually arise from multipotent stem cells closely associated with hair follicles.

The cutaneous neurofibromas never become malignant. Nevertheless, they have a huge negative impact on quality of life, she said.

Patients consider cutaneous neurofibromas to be the greatest burden of NF1 because they are painful and unsightly. Dermatologists can do patients a great service by removing the benign cutaneous tumors, said Dr. Peltonen. The CO2 laser is effective for this purpose. Dozens of tumors can be removed under local anesthesia in one appointment, and patients are very appreciative. Dr. Peltonen has one patient who travels 9 hours each way for excision of cutaneous neurofibromas.

"I usually make a circle around the tumor and then cut in between dermis and the tumor while pulling on it at the same time," she said. "It’s quite easy to get the tumor out of the skin, and the holes heal nicely."

Numerous cancer drugs have been studied and found wanting for the treatment of plexiform neuromas and/or malignant peripheral nerve sheath tumors. Among the agents that have failed are sirolimus, sorafenib, erlotinib, sunitinib, ranibizumab, and cediranib. Imatinib has shown mixed results for the treatment of plexiform neuromas; a clinical trial is ongoing.

Disclosures: Dr. Peltonen said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN - Neurofibromatosis type 1 is a diagnosis every dermatologist should be able to make, according to Dr. Sirkku Peltonen.

Be sure to check the armpits, she said. Examining the axillae in search of a few small freckles often makes the difference between diagnosing neurofibromatosis type 1 (NF1) and overlooking this cancer predisposition syndrome.

"The armpits are so easy to forget – and then you lose the chance to make the diagnosis," said Dr. Peltonen of the University of Turku (Finland).

Diagnosis of NF1 is not difficult, she said. Of children aged 6 years or older, 95% can be clinically diagnosed based on the presence of at least two of the following features: six or more café au lait spots, each more than 5 mm in their greatest diameter; axillary or inguinal freckling; a first-degree relative with NF1; or pseudoarthrosis of the tibia, a finding present in only about 3% of individuals with NF1. These four features, from a longer list of diagnostic criteria established by the National Institutes of Health, are the most relevant to dermatologists (JAMA 1997;278:51-7). The flat, pigmented café au lait macules usually appear by a child’s first birthday.

"If you see four or five café au lait spots, suspect NF1 and look for more," Dr. Peltonen said at the annual congress of the European Academy of Dermatology and Venereology.

Freckles under the armpit appear by 6 years of age. Prior to that, the diagnosis is typically made on the basis of the requisite café au lait spots in a child having a family history of NF1. However, half of patients with NF1 have a sporadic mutation and no family history of the disease, making early diagnosis considerably more difficult.

Laboratory analysis of NF1 is available in challenging cases, most of which involve young children. It is a laborious, expensive process because the NF1 gene, located on chromosome 17, band q11, is large, and hundreds of mutations have been identified to date, said Dr. Peltonen.

In her experience, laboratories vary widely in their ability to perform a high-quality analysis of mutations of the NF1 gene. She singled out the laboratories at the Ghent (Belgium) University and the University of Alabama at Birmingham as being particularly good when it comes to the diagnosis of NF1. Testing costs more than $1,300, she said.

The incidence of NF1, formerly known as von Recklinghausen’s disease, is roughly 1 in 3,000 live births, noted Dr. Peltonen. Inheritance is autosomal dominant with 100% penetrance. This means everyone who has the inherited form of NF1 ought to be readily diagnosable.

NF1 is a multisystem condition. Common features include cognitive impairment in 80% of patients, learning difficulties in 50%-60%, and speech abnormalities in 30%, as well as eye and skeletal abnormalities. Affected children are at risk for social exclusion because of their appearance. A dermatologist who diagnoses NF1 needs to be ready to make a referral to a physician who is familiar with the syndrome for regular follow-up, she said.

Children with NF1 are at 100-fold increased risk for brain tumors, compared with unaffected children. The lifetime risk of developing a malignant peripheral nerve sheath tumor is 10%-15%. Thirty percent or more of patients with NF1 have one or more plexiform neuromas, which are at risk for malignant transformation. The cancers can appear at any age, although most often not until after the teenage years.

Danger signs of malignancy in patients with NF1 include neurogenic pain in the extremities, a painful mass, or accelerated growth of an existing plexiform neuroma, she added.

The majority of adults with NF1 develop cutaneous neurofibromas. These were traditionally thought to have their origin in small dermal nerve twigs containing Schwann cells. In soon-to-be-published work, however, Dr. Peltonen and his coworkers have shown that the tumors actually arise from multipotent stem cells closely associated with hair follicles.

The cutaneous neurofibromas never become malignant. Nevertheless, they have a huge negative impact on quality of life, she said.

Patients consider cutaneous neurofibromas to be the greatest burden of NF1 because they are painful and unsightly. Dermatologists can do patients a great service by removing the benign cutaneous tumors, said Dr. Peltonen. The CO2 laser is effective for this purpose. Dozens of tumors can be removed under local anesthesia in one appointment, and patients are very appreciative. Dr. Peltonen has one patient who travels 9 hours each way for excision of cutaneous neurofibromas.

"I usually make a circle around the tumor and then cut in between dermis and the tumor while pulling on it at the same time," she said. "It’s quite easy to get the tumor out of the skin, and the holes heal nicely."

Numerous cancer drugs have been studied and found wanting for the treatment of plexiform neuromas and/or malignant peripheral nerve sheath tumors. Among the agents that have failed are sirolimus, sorafenib, erlotinib, sunitinib, ranibizumab, and cediranib. Imatinib has shown mixed results for the treatment of plexiform neuromas; a clinical trial is ongoing.

Disclosures: Dr. Peltonen said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN - Neurofibromatosis type 1 is a diagnosis every dermatologist should be able to make, according to Dr. Sirkku Peltonen.

Be sure to check the armpits, she said. Examining the axillae in search of a few small freckles often makes the difference between diagnosing neurofibromatosis type 1 (NF1) and overlooking this cancer predisposition syndrome.

"The armpits are so easy to forget – and then you lose the chance to make the diagnosis," said Dr. Peltonen of the University of Turku (Finland).

Diagnosis of NF1 is not difficult, she said. Of children aged 6 years or older, 95% can be clinically diagnosed based on the presence of at least two of the following features: six or more café au lait spots, each more than 5 mm in their greatest diameter; axillary or inguinal freckling; a first-degree relative with NF1; or pseudoarthrosis of the tibia, a finding present in only about 3% of individuals with NF1. These four features, from a longer list of diagnostic criteria established by the National Institutes of Health, are the most relevant to dermatologists (JAMA 1997;278:51-7). The flat, pigmented café au lait macules usually appear by a child’s first birthday.

"If you see four or five café au lait spots, suspect NF1 and look for more," Dr. Peltonen said at the annual congress of the European Academy of Dermatology and Venereology.

Freckles under the armpit appear by 6 years of age. Prior to that, the diagnosis is typically made on the basis of the requisite café au lait spots in a child having a family history of NF1. However, half of patients with NF1 have a sporadic mutation and no family history of the disease, making early diagnosis considerably more difficult.

Laboratory analysis of NF1 is available in challenging cases, most of which involve young children. It is a laborious, expensive process because the NF1 gene, located on chromosome 17, band q11, is large, and hundreds of mutations have been identified to date, said Dr. Peltonen.

In her experience, laboratories vary widely in their ability to perform a high-quality analysis of mutations of the NF1 gene. She singled out the laboratories at the Ghent (Belgium) University and the University of Alabama at Birmingham as being particularly good when it comes to the diagnosis of NF1. Testing costs more than $1,300, she said.

The incidence of NF1, formerly known as von Recklinghausen’s disease, is roughly 1 in 3,000 live births, noted Dr. Peltonen. Inheritance is autosomal dominant with 100% penetrance. This means everyone who has the inherited form of NF1 ought to be readily diagnosable.

NF1 is a multisystem condition. Common features include cognitive impairment in 80% of patients, learning difficulties in 50%-60%, and speech abnormalities in 30%, as well as eye and skeletal abnormalities. Affected children are at risk for social exclusion because of their appearance. A dermatologist who diagnoses NF1 needs to be ready to make a referral to a physician who is familiar with the syndrome for regular follow-up, she said.

Children with NF1 are at 100-fold increased risk for brain tumors, compared with unaffected children. The lifetime risk of developing a malignant peripheral nerve sheath tumor is 10%-15%. Thirty percent or more of patients with NF1 have one or more plexiform neuromas, which are at risk for malignant transformation. The cancers can appear at any age, although most often not until after the teenage years.

Danger signs of malignancy in patients with NF1 include neurogenic pain in the extremities, a painful mass, or accelerated growth of an existing plexiform neuroma, she added.

The majority of adults with NF1 develop cutaneous neurofibromas. These were traditionally thought to have their origin in small dermal nerve twigs containing Schwann cells. In soon-to-be-published work, however, Dr. Peltonen and his coworkers have shown that the tumors actually arise from multipotent stem cells closely associated with hair follicles.

The cutaneous neurofibromas never become malignant. Nevertheless, they have a huge negative impact on quality of life, she said.

Patients consider cutaneous neurofibromas to be the greatest burden of NF1 because they are painful and unsightly. Dermatologists can do patients a great service by removing the benign cutaneous tumors, said Dr. Peltonen. The CO2 laser is effective for this purpose. Dozens of tumors can be removed under local anesthesia in one appointment, and patients are very appreciative. Dr. Peltonen has one patient who travels 9 hours each way for excision of cutaneous neurofibromas.

"I usually make a circle around the tumor and then cut in between dermis and the tumor while pulling on it at the same time," she said. "It’s quite easy to get the tumor out of the skin, and the holes heal nicely."

Numerous cancer drugs have been studied and found wanting for the treatment of plexiform neuromas and/or malignant peripheral nerve sheath tumors. Among the agents that have failed are sirolimus, sorafenib, erlotinib, sunitinib, ranibizumab, and cediranib. Imatinib has shown mixed results for the treatment of plexiform neuromas; a clinical trial is ongoing.

Disclosures: Dr. Peltonen said she had no relevant financial conflicts.