Bruce Jancin

HOUSTON – Metformin was associated with more modest reports of pain among patients with lumbar radiculopathy.

In a retrospective case-control study presented at the annual meeting of the Endocrine Society, 46 patients who were taking metformin and sought care for lumbar radiculopathy pain averaged a 1.85-point lower score on a 0-10 point "having pain now," scale as did 94 controls, 18 of whom had type 2 diabetes. The two groups were matched for their number of pain medications. None had peripheral neuropathy or other diabetic complications, reported Dr. Magdalena Szkudlinska of the University of Arizona, Tucson.

Mechanistic studies were conducted in animal models. Other researchers have identified AMPK (adenosine monophosphate–activated protein kinase) as a potential therapeutic target in chronic neuropathic pain conditions. The proposed mechanism involves activation of AMPK by metformin, with resultant inhibition of the mTOR (mammalian target of rapamycin) pathway leading to reduced sensory neuron excitability and decreased chronic neuropathic pain (Nat. Cell Biol. 2011;13:1016-23).

Moreover, Dr. Szkudlinska added, metformin has proved "remarkably effective" in reducing nociceptor sensitization and pain in animal models (Mol. Pain 2011 Sept. 21 [doi:10.1186/1744-8069-7-70]).

"We propose that these results, combined with the preclinical rationale, warrant a larger prospective study testing the effectiveness of metformin on chronic neuropathic pain," she declared.

Her retrospective lumbar radiculopathy study was supported by the National Institutes of Health. She declared having no financial conflicts.

HOUSTON – Metformin was associated with more modest reports of pain among patients with lumbar radiculopathy.

In a retrospective case-control study presented at the annual meeting of the Endocrine Society, 46 patients who were taking metformin and sought care for lumbar radiculopathy pain averaged a 1.85-point lower score on a 0-10 point "having pain now," scale as did 94 controls, 18 of whom had type 2 diabetes. The two groups were matched for their number of pain medications. None had peripheral neuropathy or other diabetic complications, reported Dr. Magdalena Szkudlinska of the University of Arizona, Tucson.

Mechanistic studies were conducted in animal models. Other researchers have identified AMPK (adenosine monophosphate–activated protein kinase) as a potential therapeutic target in chronic neuropathic pain conditions. The proposed mechanism involves activation of AMPK by metformin, with resultant inhibition of the mTOR (mammalian target of rapamycin) pathway leading to reduced sensory neuron excitability and decreased chronic neuropathic pain (Nat. Cell Biol. 2011;13:1016-23).

Moreover, Dr. Szkudlinska added, metformin has proved "remarkably effective" in reducing nociceptor sensitization and pain in animal models (Mol. Pain 2011 Sept. 21 [doi:10.1186/1744-8069-7-70]).

"We propose that these results, combined with the preclinical rationale, warrant a larger prospective study testing the effectiveness of metformin on chronic neuropathic pain," she declared.

Her retrospective lumbar radiculopathy study was supported by the National Institutes of Health. She declared having no financial conflicts.

HOUSTON – Metformin was associated with more modest reports of pain among patients with lumbar radiculopathy.

In a retrospective case-control study presented at the annual meeting of the Endocrine Society, 46 patients who were taking metformin and sought care for lumbar radiculopathy pain averaged a 1.85-point lower score on a 0-10 point "having pain now," scale as did 94 controls, 18 of whom had type 2 diabetes. The two groups were matched for their number of pain medications. None had peripheral neuropathy or other diabetic complications, reported Dr. Magdalena Szkudlinska of the University of Arizona, Tucson.

Mechanistic studies were conducted in animal models. Other researchers have identified AMPK (adenosine monophosphate–activated protein kinase) as a potential therapeutic target in chronic neuropathic pain conditions. The proposed mechanism involves activation of AMPK by metformin, with resultant inhibition of the mTOR (mammalian target of rapamycin) pathway leading to reduced sensory neuron excitability and decreased chronic neuropathic pain (Nat. Cell Biol. 2011;13:1016-23).

Moreover, Dr. Szkudlinska added, metformin has proved "remarkably effective" in reducing nociceptor sensitization and pain in animal models (Mol. Pain 2011 Sept. 21 [doi:10.1186/1744-8069-7-70]).

"We propose that these results, combined with the preclinical rationale, warrant a larger prospective study testing the effectiveness of metformin on chronic neuropathic pain," she declared.

Her retrospective lumbar radiculopathy study was supported by the National Institutes of Health. She declared having no financial conflicts.

HOUSTON – Patients with surgically treated hyperthyroidism have a lingering elevation in cardiovascular risk that persists for at least 2 decades post thyroidectomy, according to a Finnish national study.

“This is the first study to show increased risk of hospitalization for cardiovascular disease after thyroid surgery. The elevated risk is sustained 20 years after surgery. This is in line with previous studies done in patients treated with radioactive iodine. Thus, it’s probably the disease rather than the treatment that affects the patient’s heart permanently,” said Dr. Saara Metso of Tampere (Finland) University Hospital.

At the annual meeting of the Endocrine Society, she presented a population-based cohort study involving 4,334 hyperthyroid patients treated with thyroidectomy at any hospital in Finland during 1986-2007, along with 12,991 controls drawn from the general population.

The hospitalization rate for all cardiovascular causes during a median 10.5 years of follow-up was 240.5 per 10,000 person-years in the thyroidectomy group, compared with 206.2 per 10,000 person-years among controls.

These rates translated into a highly significant 17% increased risk of cardiovascular hospitalization in patients after they have undergone thyroidectomy. The risk, however, was not elevated across the board for all forms of cardiovascular disease. For example, there was no significant difference between patients and controls in hospitalization rates for coronary artery disease, cerebrovascular disease, or heart failure. On the other hand, patients with surgically treated hyperthyroidism had a 27% greater rate of hospitalization for hypertension; a 51% increase in admissions for atrial fibrillation; and a 54% greater hospitalization rate for nonbacterial endo-, peri- and myocardial diseases, valvular diseases, and cardiomyopathy, she continued.

Dr. Metso noted that a recent meta-analysis of six studies featuring long-term follow-up of patients treated for hyperthyroidism showed that the subjects had a 19% increase in cardiovascular mortality relative to age- and sex-matched controls (Eur. J. Endocrinol. 2011;165:491-7). However, most of these patients had been treated with radioiodine. This is what prompted Dr. Metso and her coinvestigators to take a close look at surgically treated patients. The most common causes of their surgically treated hyperthyroidism were Graves disease in 48% of patients, multinodular goiter in 33%, and toxic adenoma in 6%.

Several audience members, while quick to praise the Finnish study as an important advance in the field, expressed a wish that Dr. Metso and her coworkers would have included radioiodine-treated hyperthyroid patients as a control group. Audience members also would have welcomed information on postthyroidectomy thyroid replacement hormone dosing to assess whether that could be a potential contributor to the observed increase in cardiovascular risk in thyroidectomized patients.

“It’s hard to understand how the adverse cardiovascular effects could last 2 decades after the end of hyperthyroidism,” one physician commented.

The Finnish national study was funded by the Pirkanmaa Hospital Research Fund. Dr. Metso reported having no financial conflicts.

HOUSTON – Patients with surgically treated hyperthyroidism have a lingering elevation in cardiovascular risk that persists for at least 2 decades post thyroidectomy, according to a Finnish national study.

“This is the first study to show increased risk of hospitalization for cardiovascular disease after thyroid surgery. The elevated risk is sustained 20 years after surgery. This is in line with previous studies done in patients treated with radioactive iodine. Thus, it’s probably the disease rather than the treatment that affects the patient’s heart permanently,” said Dr. Saara Metso of Tampere (Finland) University Hospital.

At the annual meeting of the Endocrine Society, she presented a population-based cohort study involving 4,334 hyperthyroid patients treated with thyroidectomy at any hospital in Finland during 1986-2007, along with 12,991 controls drawn from the general population.

The hospitalization rate for all cardiovascular causes during a median 10.5 years of follow-up was 240.5 per 10,000 person-years in the thyroidectomy group, compared with 206.2 per 10,000 person-years among controls.

These rates translated into a highly significant 17% increased risk of cardiovascular hospitalization in patients after they have undergone thyroidectomy. The risk, however, was not elevated across the board for all forms of cardiovascular disease. For example, there was no significant difference between patients and controls in hospitalization rates for coronary artery disease, cerebrovascular disease, or heart failure. On the other hand, patients with surgically treated hyperthyroidism had a 27% greater rate of hospitalization for hypertension; a 51% increase in admissions for atrial fibrillation; and a 54% greater hospitalization rate for nonbacterial endo-, peri- and myocardial diseases, valvular diseases, and cardiomyopathy, she continued.

Dr. Metso noted that a recent meta-analysis of six studies featuring long-term follow-up of patients treated for hyperthyroidism showed that the subjects had a 19% increase in cardiovascular mortality relative to age- and sex-matched controls (Eur. J. Endocrinol. 2011;165:491-7). However, most of these patients had been treated with radioiodine. This is what prompted Dr. Metso and her coinvestigators to take a close look at surgically treated patients. The most common causes of their surgically treated hyperthyroidism were Graves disease in 48% of patients, multinodular goiter in 33%, and toxic adenoma in 6%.

Several audience members, while quick to praise the Finnish study as an important advance in the field, expressed a wish that Dr. Metso and her coworkers would have included radioiodine-treated hyperthyroid patients as a control group. Audience members also would have welcomed information on postthyroidectomy thyroid replacement hormone dosing to assess whether that could be a potential contributor to the observed increase in cardiovascular risk in thyroidectomized patients.

“It’s hard to understand how the adverse cardiovascular effects could last 2 decades after the end of hyperthyroidism,” one physician commented.

The Finnish national study was funded by the Pirkanmaa Hospital Research Fund. Dr. Metso reported having no financial conflicts.

HOUSTON – Patients with surgically treated hyperthyroidism have a lingering elevation in cardiovascular risk that persists for at least 2 decades post thyroidectomy, according to a Finnish national study.

“This is the first study to show increased risk of hospitalization for cardiovascular disease after thyroid surgery. The elevated risk is sustained 20 years after surgery. This is in line with previous studies done in patients treated with radioactive iodine. Thus, it’s probably the disease rather than the treatment that affects the patient’s heart permanently,” said Dr. Saara Metso of Tampere (Finland) University Hospital.

At the annual meeting of the Endocrine Society, she presented a population-based cohort study involving 4,334 hyperthyroid patients treated with thyroidectomy at any hospital in Finland during 1986-2007, along with 12,991 controls drawn from the general population.

The hospitalization rate for all cardiovascular causes during a median 10.5 years of follow-up was 240.5 per 10,000 person-years in the thyroidectomy group, compared with 206.2 per 10,000 person-years among controls.

These rates translated into a highly significant 17% increased risk of cardiovascular hospitalization in patients after they have undergone thyroidectomy. The risk, however, was not elevated across the board for all forms of cardiovascular disease. For example, there was no significant difference between patients and controls in hospitalization rates for coronary artery disease, cerebrovascular disease, or heart failure. On the other hand, patients with surgically treated hyperthyroidism had a 27% greater rate of hospitalization for hypertension; a 51% increase in admissions for atrial fibrillation; and a 54% greater hospitalization rate for nonbacterial endo-, peri- and myocardial diseases, valvular diseases, and cardiomyopathy, she continued.

Dr. Metso noted that a recent meta-analysis of six studies featuring long-term follow-up of patients treated for hyperthyroidism showed that the subjects had a 19% increase in cardiovascular mortality relative to age- and sex-matched controls (Eur. J. Endocrinol. 2011;165:491-7). However, most of these patients had been treated with radioiodine. This is what prompted Dr. Metso and her coinvestigators to take a close look at surgically treated patients. The most common causes of their surgically treated hyperthyroidism were Graves disease in 48% of patients, multinodular goiter in 33%, and toxic adenoma in 6%.

Several audience members, while quick to praise the Finnish study as an important advance in the field, expressed a wish that Dr. Metso and her coworkers would have included radioiodine-treated hyperthyroid patients as a control group. Audience members also would have welcomed information on postthyroidectomy thyroid replacement hormone dosing to assess whether that could be a potential contributor to the observed increase in cardiovascular risk in thyroidectomized patients.

“It’s hard to understand how the adverse cardiovascular effects could last 2 decades after the end of hyperthyroidism,” one physician commented.

The Finnish national study was funded by the Pirkanmaa Hospital Research Fund. Dr. Metso reported having no financial conflicts.

HOUSTON – Hypoparathyroidism may soon lose its status as the only endocrine deficiency disease for which the missing hormone isn’t available as an approved replacement therapy.

That change may come as a result of the positive findings of the REPLACE study of the investigational recombinant human parathyroid hormone (1-84), known as Natpara.

REPLACE was a double-blind, randomized, multinational, dose-escalation clinical trial of 134 adults with hypoparathyroidism. After an average 10-week stabilization period in which participants’ oral calcium and active vitamin D doses were adjusted to maintain optimal biochemical control of their disease as defined by serum calcium concentrations of 8.0-9.0 mg/dL for 2 weeks, they were randomized 2:1 to once-daily self-injected subcutaneous recombinant human parathyroid hormone (rhPTH) or placebo for 24 weeks.

The starting dose of rhPTH was 50 mcg. Subjects underwent staged reductions in their calcium and vitamin D supplementation while maintaining a serum calcium level in the target range. In order to accomplish this, patients could be up-titrated to 75 mcg and if need be 100 mcg per day over 6-8 weeks, Dr. Michael Mannstadt explained at the annual meeting of the Endocrine Society.

The primary end point in the REPLACE study was at least a 50% reduction in oral calcium and vitamin D requirements at week 24 compared with baseline, along with maintenance of serum calcium in the target range. This combined end point was achieved in 53% of patients on rhPTH, compared with 2% of controls, reported Dr. Mannstadt, of Harvard Medical School and Massachusetts General Hospital, both in Boston.

At week 24, 43% of patients in the rhPTH arm no longer required vitamin D supplementation and could be maintained on an oral calcium dose of 500 mg/day or less of calcipotriol. This secondary end point was achieved in only 5% of controls.

The mean dose of active vitamin D was reduced by 78% compared with baseline in the rhPTH group and by 30% in controls. The mean dose of oral calcium was lowered by 52% in the rhPTH group, compared with a 5.7% increase over baseline in controls.

Natpara was generally well tolerated, with adverse event rates and profiles similar to those of the placebo arm. An ongoing extension phase of the REPLACE trial is looking at the effects of treatment beyond 24 weeks.

The REPLACE participants were similar to the patients typically encountered in clinical practice. They averaged 48 years of age and had a 13-year history of hypoparathyroidism; 78% were women; and their hormone deficiency resulted from surgery in three-quarters of cases.

Symptoms of hypoparathyroidism include paresthesias, uncontrollable muscle spasms, fatigue, laryngospasm, depression, and even seizures. The impetus for developing Natpara as the first replacement therapy for hypothyroidism stems from the high rate of serious complications resulting from current therapy, which entails large doses of calcium and vitamin D. High-dose calcium supplementation can result in major swings in serum calcium levels and, long term, as calcium builds up extraskeletally, in coronary artery calcification, renal damage, and neurocognitive abnormalities, Dr. Mannstadt noted.

This study was sponsored by NPS Pharmaceuticals. Dr. Mannstadt reported that he is on the company’s advisory board.

*CORRECTION 8/2/12:  Natpara was misspelled in the headline in a previous version of this story. This version reflects the corrected headline.

HOUSTON – Hypoparathyroidism may soon lose its status as the only endocrine deficiency disease for which the missing hormone isn’t available as an approved replacement therapy.

That change may come as a result of the positive findings of the REPLACE study of the investigational recombinant human parathyroid hormone (1-84), known as Natpara.

REPLACE was a double-blind, randomized, multinational, dose-escalation clinical trial of 134 adults with hypoparathyroidism. After an average 10-week stabilization period in which participants’ oral calcium and active vitamin D doses were adjusted to maintain optimal biochemical control of their disease as defined by serum calcium concentrations of 8.0-9.0 mg/dL for 2 weeks, they were randomized 2:1 to once-daily self-injected subcutaneous recombinant human parathyroid hormone (rhPTH) or placebo for 24 weeks.

The starting dose of rhPTH was 50 mcg. Subjects underwent staged reductions in their calcium and vitamin D supplementation while maintaining a serum calcium level in the target range. In order to accomplish this, patients could be up-titrated to 75 mcg and if need be 100 mcg per day over 6-8 weeks, Dr. Michael Mannstadt explained at the annual meeting of the Endocrine Society.

The primary end point in the REPLACE study was at least a 50% reduction in oral calcium and vitamin D requirements at week 24 compared with baseline, along with maintenance of serum calcium in the target range. This combined end point was achieved in 53% of patients on rhPTH, compared with 2% of controls, reported Dr. Mannstadt, of Harvard Medical School and Massachusetts General Hospital, both in Boston.

At week 24, 43% of patients in the rhPTH arm no longer required vitamin D supplementation and could be maintained on an oral calcium dose of 500 mg/day or less of calcipotriol. This secondary end point was achieved in only 5% of controls.

The mean dose of active vitamin D was reduced by 78% compared with baseline in the rhPTH group and by 30% in controls. The mean dose of oral calcium was lowered by 52% in the rhPTH group, compared with a 5.7% increase over baseline in controls.

Natpara was generally well tolerated, with adverse event rates and profiles similar to those of the placebo arm. An ongoing extension phase of the REPLACE trial is looking at the effects of treatment beyond 24 weeks.

The REPLACE participants were similar to the patients typically encountered in clinical practice. They averaged 48 years of age and had a 13-year history of hypoparathyroidism; 78% were women; and their hormone deficiency resulted from surgery in three-quarters of cases.

Symptoms of hypoparathyroidism include paresthesias, uncontrollable muscle spasms, fatigue, laryngospasm, depression, and even seizures. The impetus for developing Natpara as the first replacement therapy for hypothyroidism stems from the high rate of serious complications resulting from current therapy, which entails large doses of calcium and vitamin D. High-dose calcium supplementation can result in major swings in serum calcium levels and, long term, as calcium builds up extraskeletally, in coronary artery calcification, renal damage, and neurocognitive abnormalities, Dr. Mannstadt noted.

This study was sponsored by NPS Pharmaceuticals. Dr. Mannstadt reported that he is on the company’s advisory board.

*CORRECTION 8/2/12:  Natpara was misspelled in the headline in a previous version of this story. This version reflects the corrected headline.

HOUSTON – Hypoparathyroidism may soon lose its status as the only endocrine deficiency disease for which the missing hormone isn’t available as an approved replacement therapy.

That change may come as a result of the positive findings of the REPLACE study of the investigational recombinant human parathyroid hormone (1-84), known as Natpara.

REPLACE was a double-blind, randomized, multinational, dose-escalation clinical trial of 134 adults with hypoparathyroidism. After an average 10-week stabilization period in which participants’ oral calcium and active vitamin D doses were adjusted to maintain optimal biochemical control of their disease as defined by serum calcium concentrations of 8.0-9.0 mg/dL for 2 weeks, they were randomized 2:1 to once-daily self-injected subcutaneous recombinant human parathyroid hormone (rhPTH) or placebo for 24 weeks.

The starting dose of rhPTH was 50 mcg. Subjects underwent staged reductions in their calcium and vitamin D supplementation while maintaining a serum calcium level in the target range. In order to accomplish this, patients could be up-titrated to 75 mcg and if need be 100 mcg per day over 6-8 weeks, Dr. Michael Mannstadt explained at the annual meeting of the Endocrine Society.

The primary end point in the REPLACE study was at least a 50% reduction in oral calcium and vitamin D requirements at week 24 compared with baseline, along with maintenance of serum calcium in the target range. This combined end point was achieved in 53% of patients on rhPTH, compared with 2% of controls, reported Dr. Mannstadt, of Harvard Medical School and Massachusetts General Hospital, both in Boston.

At week 24, 43% of patients in the rhPTH arm no longer required vitamin D supplementation and could be maintained on an oral calcium dose of 500 mg/day or less of calcipotriol. This secondary end point was achieved in only 5% of controls.

The mean dose of active vitamin D was reduced by 78% compared with baseline in the rhPTH group and by 30% in controls. The mean dose of oral calcium was lowered by 52% in the rhPTH group, compared with a 5.7% increase over baseline in controls.

Natpara was generally well tolerated, with adverse event rates and profiles similar to those of the placebo arm. An ongoing extension phase of the REPLACE trial is looking at the effects of treatment beyond 24 weeks.

The REPLACE participants were similar to the patients typically encountered in clinical practice. They averaged 48 years of age and had a 13-year history of hypoparathyroidism; 78% were women; and their hormone deficiency resulted from surgery in three-quarters of cases.

Symptoms of hypoparathyroidism include paresthesias, uncontrollable muscle spasms, fatigue, laryngospasm, depression, and even seizures. The impetus for developing Natpara as the first replacement therapy for hypothyroidism stems from the high rate of serious complications resulting from current therapy, which entails large doses of calcium and vitamin D. High-dose calcium supplementation can result in major swings in serum calcium levels and, long term, as calcium builds up extraskeletally, in coronary artery calcification, renal damage, and neurocognitive abnormalities, Dr. Mannstadt noted.

This study was sponsored by NPS Pharmaceuticals. Dr. Mannstadt reported that he is on the company’s advisory board.

*CORRECTION 8/2/12:  Natpara was misspelled in the headline in a previous version of this story. This version reflects the corrected headline.

RALEIGH, N.C. – Offering free drug samples to newly diagnosed acne patients was found to increase the likelihood of prescribing more expensive medications, according to a new study.

"The benefits of free sample distribution in dermatology clinics must be weighed against the significant negative impact that free samples have on prescribing and prescription costs. Clinical trials comparing the efficacy of new branded generic drugs with existing alternatives should increasingly be used to justify their increased retail cost," said study investigator Michael Hurley, a Stanford (Calif.) University medical student.

The investigators analyzed all prescriptions written for newly diagnosed acne patients in 2010 at two dermatology clinics, one in an academic medical center that does not allow samples, and the second at an affiliated neighborhood clinic that does.

At the no-samples clinic, 17% of prescriptions written by office-based dermatologists for acne patients at their initial office visit were for branded or branded-generic drugs, compared with a 74% rate at the neighborhood clinic allowing free samples.

The average prescription costs were also higher at the clinic that uses free samples. The average retail cost of the top 20 prescribed acne medications at each site (which collectively accounted for roughly 70% of all acne prescriptions) was $204 at the neighborhood clinic, compared with $70.49 at the clinic with no free samples. After the average number of prescriptions written per visit was taken into account, this amounted to a cost difference of about $260 per office visit, reported Mr. Hurley.

In a multivariate regression analysis accounting for patient characteristics and other potential confounding factors, dermatologists who provided free samples of acne drugs were 3.4-fold more likely to prescribe a branded or branded generic drug than a less expensive generic.

After identifying the marked difference in dermatologists’ acne drug prescribing patterns at the two clinics in Northern California, Mr. Hurley and his coinvestigators analyzed national data to establish trends.

Data from the National Disease and Therapeutic Index – a national survey of physician self-reported office visits, diagnoses, and treatments conducted by IMS Health – were assessed. The data showed that in 2010, 79% of all prescriptions written by office-based dermatologists for acne patients at their initial visit were for branded or branded-generic drugs.

The data also found that the proportion of acne prescriptions written with a free sample increased from 38% to 51% in the last decade. Prescriptions for branded generic medications rose similarly, most likely because of the increased use of free samples of those drugs, said Mr. Hurley. Meanwhile the percentage of acne prescriptions for generic drugs has remained flat, and in absolute numbers has actually decreased, he said.

Upon close scrutiny of dermatologists’ acne prescribing nationally in 2010, 2005, and 2001, Mr. Hurley concluded that although dermatologists’ drug preferences do change over time as new medications enter the market, their prescribing consistently remains closely related to what’s available as a free sample.

For example, during 2010 the top five acne medications prescribed by dermatologists were (in descending order) Epiduo, doxycycline hyclate, Metrogel, Solodyn, and Differin. The top five prescribed with a free sample were Epiduo, Metrogel, Solodyn, Ziana, and Oracea.

The top five agents prescribed overall in 2005 were Differin, Benzaclin, Duac, Retin-A-Micro, and doxycycline hyclate, whereas the top five prescribed with a free sample during that year were Differin, Duac, Benzaclin, Retin-A-Micro, and Metrogel.

Mr. Hurley reported having no financial conflicts.

RALEIGH, N.C. – Offering free drug samples to newly diagnosed acne patients was found to increase the likelihood of prescribing more expensive medications, according to a new study.

"The benefits of free sample distribution in dermatology clinics must be weighed against the significant negative impact that free samples have on prescribing and prescription costs. Clinical trials comparing the efficacy of new branded generic drugs with existing alternatives should increasingly be used to justify their increased retail cost," said study investigator Michael Hurley, a Stanford (Calif.) University medical student.

The investigators analyzed all prescriptions written for newly diagnosed acne patients in 2010 at two dermatology clinics, one in an academic medical center that does not allow samples, and the second at an affiliated neighborhood clinic that does.

At the no-samples clinic, 17% of prescriptions written by office-based dermatologists for acne patients at their initial office visit were for branded or branded-generic drugs, compared with a 74% rate at the neighborhood clinic allowing free samples.

The average prescription costs were also higher at the clinic that uses free samples. The average retail cost of the top 20 prescribed acne medications at each site (which collectively accounted for roughly 70% of all acne prescriptions) was $204 at the neighborhood clinic, compared with $70.49 at the clinic with no free samples. After the average number of prescriptions written per visit was taken into account, this amounted to a cost difference of about $260 per office visit, reported Mr. Hurley.

In a multivariate regression analysis accounting for patient characteristics and other potential confounding factors, dermatologists who provided free samples of acne drugs were 3.4-fold more likely to prescribe a branded or branded generic drug than a less expensive generic.

After identifying the marked difference in dermatologists’ acne drug prescribing patterns at the two clinics in Northern California, Mr. Hurley and his coinvestigators analyzed national data to establish trends.

Data from the National Disease and Therapeutic Index – a national survey of physician self-reported office visits, diagnoses, and treatments conducted by IMS Health – were assessed. The data showed that in 2010, 79% of all prescriptions written by office-based dermatologists for acne patients at their initial visit were for branded or branded-generic drugs.

The data also found that the proportion of acne prescriptions written with a free sample increased from 38% to 51% in the last decade. Prescriptions for branded generic medications rose similarly, most likely because of the increased use of free samples of those drugs, said Mr. Hurley. Meanwhile the percentage of acne prescriptions for generic drugs has remained flat, and in absolute numbers has actually decreased, he said.

Upon close scrutiny of dermatologists’ acne prescribing nationally in 2010, 2005, and 2001, Mr. Hurley concluded that although dermatologists’ drug preferences do change over time as new medications enter the market, their prescribing consistently remains closely related to what’s available as a free sample.

For example, during 2010 the top five acne medications prescribed by dermatologists were (in descending order) Epiduo, doxycycline hyclate, Metrogel, Solodyn, and Differin. The top five prescribed with a free sample were Epiduo, Metrogel, Solodyn, Ziana, and Oracea.

The top five agents prescribed overall in 2005 were Differin, Benzaclin, Duac, Retin-A-Micro, and doxycycline hyclate, whereas the top five prescribed with a free sample during that year were Differin, Duac, Benzaclin, Retin-A-Micro, and Metrogel.

Mr. Hurley reported having no financial conflicts.

RALEIGH, N.C. – Offering free drug samples to newly diagnosed acne patients was found to increase the likelihood of prescribing more expensive medications, according to a new study.

"The benefits of free sample distribution in dermatology clinics must be weighed against the significant negative impact that free samples have on prescribing and prescription costs. Clinical trials comparing the efficacy of new branded generic drugs with existing alternatives should increasingly be used to justify their increased retail cost," said study investigator Michael Hurley, a Stanford (Calif.) University medical student.

The investigators analyzed all prescriptions written for newly diagnosed acne patients in 2010 at two dermatology clinics, one in an academic medical center that does not allow samples, and the second at an affiliated neighborhood clinic that does.

At the no-samples clinic, 17% of prescriptions written by office-based dermatologists for acne patients at their initial office visit were for branded or branded-generic drugs, compared with a 74% rate at the neighborhood clinic allowing free samples.

The average prescription costs were also higher at the clinic that uses free samples. The average retail cost of the top 20 prescribed acne medications at each site (which collectively accounted for roughly 70% of all acne prescriptions) was $204 at the neighborhood clinic, compared with $70.49 at the clinic with no free samples. After the average number of prescriptions written per visit was taken into account, this amounted to a cost difference of about $260 per office visit, reported Mr. Hurley.

In a multivariate regression analysis accounting for patient characteristics and other potential confounding factors, dermatologists who provided free samples of acne drugs were 3.4-fold more likely to prescribe a branded or branded generic drug than a less expensive generic.

After identifying the marked difference in dermatologists’ acne drug prescribing patterns at the two clinics in Northern California, Mr. Hurley and his coinvestigators analyzed national data to establish trends.

Data from the National Disease and Therapeutic Index – a national survey of physician self-reported office visits, diagnoses, and treatments conducted by IMS Health – were assessed. The data showed that in 2010, 79% of all prescriptions written by office-based dermatologists for acne patients at their initial visit were for branded or branded-generic drugs.

The data also found that the proportion of acne prescriptions written with a free sample increased from 38% to 51% in the last decade. Prescriptions for branded generic medications rose similarly, most likely because of the increased use of free samples of those drugs, said Mr. Hurley. Meanwhile the percentage of acne prescriptions for generic drugs has remained flat, and in absolute numbers has actually decreased, he said.

Upon close scrutiny of dermatologists’ acne prescribing nationally in 2010, 2005, and 2001, Mr. Hurley concluded that although dermatologists’ drug preferences do change over time as new medications enter the market, their prescribing consistently remains closely related to what’s available as a free sample.

For example, during 2010 the top five acne medications prescribed by dermatologists were (in descending order) Epiduo, doxycycline hyclate, Metrogel, Solodyn, and Differin. The top five prescribed with a free sample were Epiduo, Metrogel, Solodyn, Ziana, and Oracea.

The top five agents prescribed overall in 2005 were Differin, Benzaclin, Duac, Retin-A-Micro, and doxycycline hyclate, whereas the top five prescribed with a free sample during that year were Differin, Duac, Benzaclin, Retin-A-Micro, and Metrogel.

Mr. Hurley reported having no financial conflicts.

RALEIGH, N.C. – The incidence of invasive squamous cell carcinoma has more than doubled among U.S. nonphysician health professionals in the last 20 years, with marked sex differences evident in body-site distribution.

Dr. Khang Nguyen said his meta-analysis of data drawn from the Nurses' Health Study, the Nurses' Health Study II, and the Health Professionals Follow-Up Study was spurred by the fact that the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) database and other national databases that record cancer statistics don’t track squamous cell carcinoma (SCC).

"Much of what we know about the epidemiology of squamous cell carcinoma comes from studies from the 1990s and earlier," noted Dr. Nguyen of Brigham and Women’s Hospital, Boston.

To help rectify this situation, he and his coinvestigators analyzed cases of pathologist-confirmed invasive SCC in the roughly 121,000 female participants in the Nurses’ Health Study, the 117,000 in the Nurses’ Health Study II, and 51,000 men in the Health Professionals Follow-Up Study. There were 1,580 cases in the Nurses’ Health Study, 468 in the Nurses’ Health Study II, and 1,194 in the Health Professionals Follow-Up Study.

Among participants in the Nurses’ Health Study, the incidence of invasive SCC climbed from 40 per 100,000 person-years in 1987 to a peak of 120 per 100,000 person-years in 2005 before declining to 80 per 100,000 in 2007. Rates were lower in the Nurses’ Health Study II, a younger cohort. Among men in the Health Professionals Follow-Up Study, the incidence was 80 per 100,000 person-years in 1987, peaking at more than 160 per 100,000 person-years in 2002, and then falling back slightly to 140 per 100,000 person-years in 2007.

Invasive SCC occurred more often in the head and neck region among men, and in the thigh, buttock, legs, and feet region in women.

The significant risk factors for the malignancy, which emerged from a multivariate logistic regression analysis, included a history of painful or blistering sunburns (with an associated 2.2-fold increased risk) and a history of six or more sunburns in childhood. Other independent risk factors for invasive SCC were a family history of melanoma and lighter hair color.

The Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-Up Study were funded by the National Institutes of Health. Dr. Nguyen’s analysis was funded in part by a grant from the Doris Duke Charitable Foundation.

RALEIGH, N.C. – The incidence of invasive squamous cell carcinoma has more than doubled among U.S. nonphysician health professionals in the last 20 years, with marked sex differences evident in body-site distribution.

Dr. Khang Nguyen said his meta-analysis of data drawn from the Nurses' Health Study, the Nurses' Health Study II, and the Health Professionals Follow-Up Study was spurred by the fact that the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) database and other national databases that record cancer statistics don’t track squamous cell carcinoma (SCC).

"Much of what we know about the epidemiology of squamous cell carcinoma comes from studies from the 1990s and earlier," noted Dr. Nguyen of Brigham and Women’s Hospital, Boston.

To help rectify this situation, he and his coinvestigators analyzed cases of pathologist-confirmed invasive SCC in the roughly 121,000 female participants in the Nurses’ Health Study, the 117,000 in the Nurses’ Health Study II, and 51,000 men in the Health Professionals Follow-Up Study. There were 1,580 cases in the Nurses’ Health Study, 468 in the Nurses’ Health Study II, and 1,194 in the Health Professionals Follow-Up Study.

Among participants in the Nurses’ Health Study, the incidence of invasive SCC climbed from 40 per 100,000 person-years in 1987 to a peak of 120 per 100,000 person-years in 2005 before declining to 80 per 100,000 in 2007. Rates were lower in the Nurses’ Health Study II, a younger cohort. Among men in the Health Professionals Follow-Up Study, the incidence was 80 per 100,000 person-years in 1987, peaking at more than 160 per 100,000 person-years in 2002, and then falling back slightly to 140 per 100,000 person-years in 2007.

Invasive SCC occurred more often in the head and neck region among men, and in the thigh, buttock, legs, and feet region in women.

The significant risk factors for the malignancy, which emerged from a multivariate logistic regression analysis, included a history of painful or blistering sunburns (with an associated 2.2-fold increased risk) and a history of six or more sunburns in childhood. Other independent risk factors for invasive SCC were a family history of melanoma and lighter hair color.

The Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-Up Study were funded by the National Institutes of Health. Dr. Nguyen’s analysis was funded in part by a grant from the Doris Duke Charitable Foundation.

RALEIGH, N.C. – The incidence of invasive squamous cell carcinoma has more than doubled among U.S. nonphysician health professionals in the last 20 years, with marked sex differences evident in body-site distribution.

Dr. Khang Nguyen said his meta-analysis of data drawn from the Nurses' Health Study, the Nurses' Health Study II, and the Health Professionals Follow-Up Study was spurred by the fact that the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) database and other national databases that record cancer statistics don’t track squamous cell carcinoma (SCC).

"Much of what we know about the epidemiology of squamous cell carcinoma comes from studies from the 1990s and earlier," noted Dr. Nguyen of Brigham and Women’s Hospital, Boston.

To help rectify this situation, he and his coinvestigators analyzed cases of pathologist-confirmed invasive SCC in the roughly 121,000 female participants in the Nurses’ Health Study, the 117,000 in the Nurses’ Health Study II, and 51,000 men in the Health Professionals Follow-Up Study. There were 1,580 cases in the Nurses’ Health Study, 468 in the Nurses’ Health Study II, and 1,194 in the Health Professionals Follow-Up Study.

Among participants in the Nurses’ Health Study, the incidence of invasive SCC climbed from 40 per 100,000 person-years in 1987 to a peak of 120 per 100,000 person-years in 2005 before declining to 80 per 100,000 in 2007. Rates were lower in the Nurses’ Health Study II, a younger cohort. Among men in the Health Professionals Follow-Up Study, the incidence was 80 per 100,000 person-years in 1987, peaking at more than 160 per 100,000 person-years in 2002, and then falling back slightly to 140 per 100,000 person-years in 2007.

Invasive SCC occurred more often in the head and neck region among men, and in the thigh, buttock, legs, and feet region in women.

The significant risk factors for the malignancy, which emerged from a multivariate logistic regression analysis, included a history of painful or blistering sunburns (with an associated 2.2-fold increased risk) and a history of six or more sunburns in childhood. Other independent risk factors for invasive SCC were a family history of melanoma and lighter hair color.

The Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-Up Study were funded by the National Institutes of Health. Dr. Nguyen’s analysis was funded in part by a grant from the Doris Duke Charitable Foundation.

HOUSTON – Glipizide, glyburide, and glimepiride were independently associated with 59%-68% greater all-cause mortality risks than metformin in a retrospective study of nearly 24,000 type 2 diabetic patients on monotherapy for control of blood sugar.

Notably, among the 2,721 subjects with documented coronary artery disease (CAD), glipizide and glyburide carried an increased overall mortality risk compared with metformin, but glimepiride did not, according to Dr. Kevin M. Pantalone of Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"Metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes. Our results suggest that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred sulfonylurea in those with known coronary artery disease," he said at the annual meeting of the Endocrine Society.

Given that this was a retrospective study, it has to be viewed as hypothesis generating. A prospective study is warranted to establish the causal mechanism for the observed increase in mortality risk associated with these three widely prescribed sulfonylureas.

"The Food and Drug Administration now requires all drugs for the treatment of diabetes to have a cardiovascular safety study. These older drugs, which are considered tier 1, core-validated therapies by the American Diabetes Association, appear to have been given a free pass in terms of their cardiovascular risk," the endocrinologist observed.

He reported on 23,915 patients with type 2 diabetes who began monotherapy with metformin or one of the three sulfonylureas. The study was conducted using data from the Cleveland Clinic’s electronic health record system. Patients were followed for a median of 2.2 years, during which 2,546 deaths occurred in 58,513 person-years of follow-up.

In a multivariate Cox regression analysis adjusted for 16 variables, glipizide was independently associated with a 64% greater relative risk of all-cause mortality than was metformin. Glyburide was linked to a 59% increased risk, and glimepiride was associated with a 68% increased risk.

Among 2,721 diabetic patients with documented baseline CAD, there were 419 deaths during 5,980 person-years of follow-up. In this subgroup with CAD, glipizide had a 41% increased overall mortality risk, and glyburide had a 38% greater risk than metformin.

The clinical implications of these study findings are huge, Dr. Pantalone said. An estimated 26 million Americans have diabetes, and most of them either have known CAD or are at elevated risk for it. The four antidiabetic drugs examined in the study are among the most widely prescribed agents for blood glucose control, and all four are available in generic versions at bargain basement prices.

Dr. Alvin Powers commented that controversy surrounding the safety of sulfonylureas dates back several decades. As far as he’s concerned the issue remains unresolved, given the limitations of Dr. Pantalone’s retrospective study design.

"I think we really need a prospective comparison. I think metformin remains the primary drug, and when we add a second-line drug, the studies would show that glipizide and glimepiride are probably preferred over glyburide because of the length of time they’ve been studied. But I think that because glycemic control is important, the second-line drug still can be a sulfonylurea," said Dr. Powers, professor of medicine at Vanderbilt University, Nashville, Tenn., and director of the Vanderbilt Diabetes Center.

Dr. Pantalone’s study was supported by a research grant from AstraZeneca.

HOUSTON – Glipizide, glyburide, and glimepiride were independently associated with 59%-68% greater all-cause mortality risks than metformin in a retrospective study of nearly 24,000 type 2 diabetic patients on monotherapy for control of blood sugar.

Notably, among the 2,721 subjects with documented coronary artery disease (CAD), glipizide and glyburide carried an increased overall mortality risk compared with metformin, but glimepiride did not, according to Dr. Kevin M. Pantalone of Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"Metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes. Our results suggest that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred sulfonylurea in those with known coronary artery disease," he said at the annual meeting of the Endocrine Society.

Given that this was a retrospective study, it has to be viewed as hypothesis generating. A prospective study is warranted to establish the causal mechanism for the observed increase in mortality risk associated with these three widely prescribed sulfonylureas.

"The Food and Drug Administration now requires all drugs for the treatment of diabetes to have a cardiovascular safety study. These older drugs, which are considered tier 1, core-validated therapies by the American Diabetes Association, appear to have been given a free pass in terms of their cardiovascular risk," the endocrinologist observed.

He reported on 23,915 patients with type 2 diabetes who began monotherapy with metformin or one of the three sulfonylureas. The study was conducted using data from the Cleveland Clinic’s electronic health record system. Patients were followed for a median of 2.2 years, during which 2,546 deaths occurred in 58,513 person-years of follow-up.

In a multivariate Cox regression analysis adjusted for 16 variables, glipizide was independently associated with a 64% greater relative risk of all-cause mortality than was metformin. Glyburide was linked to a 59% increased risk, and glimepiride was associated with a 68% increased risk.

Among 2,721 diabetic patients with documented baseline CAD, there were 419 deaths during 5,980 person-years of follow-up. In this subgroup with CAD, glipizide had a 41% increased overall mortality risk, and glyburide had a 38% greater risk than metformin.

The clinical implications of these study findings are huge, Dr. Pantalone said. An estimated 26 million Americans have diabetes, and most of them either have known CAD or are at elevated risk for it. The four antidiabetic drugs examined in the study are among the most widely prescribed agents for blood glucose control, and all four are available in generic versions at bargain basement prices.

Dr. Alvin Powers commented that controversy surrounding the safety of sulfonylureas dates back several decades. As far as he’s concerned the issue remains unresolved, given the limitations of Dr. Pantalone’s retrospective study design.

"I think we really need a prospective comparison. I think metformin remains the primary drug, and when we add a second-line drug, the studies would show that glipizide and glimepiride are probably preferred over glyburide because of the length of time they’ve been studied. But I think that because glycemic control is important, the second-line drug still can be a sulfonylurea," said Dr. Powers, professor of medicine at Vanderbilt University, Nashville, Tenn., and director of the Vanderbilt Diabetes Center.

Dr. Pantalone’s study was supported by a research grant from AstraZeneca.

HOUSTON – Glipizide, glyburide, and glimepiride were independently associated with 59%-68% greater all-cause mortality risks than metformin in a retrospective study of nearly 24,000 type 2 diabetic patients on monotherapy for control of blood sugar.

Notably, among the 2,721 subjects with documented coronary artery disease (CAD), glipizide and glyburide carried an increased overall mortality risk compared with metformin, but glimepiride did not, according to Dr. Kevin M. Pantalone of Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"Metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes. Our results suggest that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred sulfonylurea in those with known coronary artery disease," he said at the annual meeting of the Endocrine Society.

Given that this was a retrospective study, it has to be viewed as hypothesis generating. A prospective study is warranted to establish the causal mechanism for the observed increase in mortality risk associated with these three widely prescribed sulfonylureas.

"The Food and Drug Administration now requires all drugs for the treatment of diabetes to have a cardiovascular safety study. These older drugs, which are considered tier 1, core-validated therapies by the American Diabetes Association, appear to have been given a free pass in terms of their cardiovascular risk," the endocrinologist observed.

He reported on 23,915 patients with type 2 diabetes who began monotherapy with metformin or one of the three sulfonylureas. The study was conducted using data from the Cleveland Clinic’s electronic health record system. Patients were followed for a median of 2.2 years, during which 2,546 deaths occurred in 58,513 person-years of follow-up.

In a multivariate Cox regression analysis adjusted for 16 variables, glipizide was independently associated with a 64% greater relative risk of all-cause mortality than was metformin. Glyburide was linked to a 59% increased risk, and glimepiride was associated with a 68% increased risk.

Among 2,721 diabetic patients with documented baseline CAD, there were 419 deaths during 5,980 person-years of follow-up. In this subgroup with CAD, glipizide had a 41% increased overall mortality risk, and glyburide had a 38% greater risk than metformin.

The clinical implications of these study findings are huge, Dr. Pantalone said. An estimated 26 million Americans have diabetes, and most of them either have known CAD or are at elevated risk for it. The four antidiabetic drugs examined in the study are among the most widely prescribed agents for blood glucose control, and all four are available in generic versions at bargain basement prices.

Dr. Alvin Powers commented that controversy surrounding the safety of sulfonylureas dates back several decades. As far as he’s concerned the issue remains unresolved, given the limitations of Dr. Pantalone’s retrospective study design.

"I think we really need a prospective comparison. I think metformin remains the primary drug, and when we add a second-line drug, the studies would show that glipizide and glimepiride are probably preferred over glyburide because of the length of time they’ve been studied. But I think that because glycemic control is important, the second-line drug still can be a sulfonylurea," said Dr. Powers, professor of medicine at Vanderbilt University, Nashville, Tenn., and director of the Vanderbilt Diabetes Center.

Dr. Pantalone’s study was supported by a research grant from AstraZeneca.

RALEIGH, N.C. – The ratio of melanoma in situ to invasive melanoma jumped 12-fold among American health professionals during a recent 3-decade period.

Just how much of this steep rise in melanoma in situ diagnoses represents a true increase in the development of in situ lesions as opposed to the product of improved screening techniques or overdiagnosis due to medicolegal pressure remains a matter for conjecture. The new analysis of melanoma trends in the Nurses' Health Study and the Health Professionals Follow-Up Study provides evidence suggesting that all three factors may be involved, according to Erin X. Wei of Massachusetts General Hospital, Boston.

Her analysis included roughly 121,000 female nurses followed prospectively in the Nurses’ Health Study since 1976 and 51,000 men followed in the Health Professionals Follow-Up Study since 1986. During the follow-up period, new cases of invasive melanoma increased dramatically, but they were far outpaced by the rise in cases of melanoma in situ, she said at the annual meeting of the Society for Investigative Dermatology.

For example, while the ratio of in situ to invasive melanoma among women was 0.09:1 in 1977, by 2002 it had reached 1:1.

Support for the notion that the rise in melanoma in situ is due in part to overdiagnosis in response to medicolegal concerns comes from the finding that the bulk of the increase involves lesions reported in this study as having Not-Otherwise-Specified pathology. Lentigo maligna cases have remained relatively flat over time, she noted.

Also, in this large patient population, as well as in studies from elsewhere around the world, the increase in melanoma in situ has not been accompanied by a shift in the pattern of invasive melanoma thickness or by a reduction in melanoma mortality, as would be expected in response to a major increase in detection of invasive melanoma precursor lesions.

But perhaps in situ melanomas are often not precursors to invasive melanoma. If they were precursors, one would expect them to be diagnosed at a younger average age than invasive melanoma. Such was not the case in this analysis. Indeed, while roughly 40% of invasive melanomas were diagnosed prior to age 60, that was true for only 20% of melanoma in situ. Nurses diagnosed with melanoma in situ were an average of 6 years older than those diagnosed with invasive melanoma; among men, the difference was 2 years.

Melanoma in situ and invasive melanomas tended to differ in their anatomic distribution. Invasive melanomas were far less likely than in situ lesions to occur on the head and neck, and much more likely to occur on the lower extremities. This suggests some in situ melanomas are indolent and do not become malignant over time, Ms. Wei continued.

In support of the existence of a true biologic increase in the incidence of melanoma in situ, Ms. Wei and her coworkers found that older individuals were two- to threefold more likely to develop their lesions on chronically sun-exposed areas than on intermittently sun-exposed areas.

An intriguing gender difference in the anatomic distribution of melanoma in situ was evident. Among men, more than 98% of all melanoma in situ were found on the upper half of the body. In women, the lesions were more evenly distributed anatomically, with 27% of in situ lesions being found on the lower extremities.

The Nurses’ Health Study and Health Professionals Follow-up Study are funded by the National Institutes of Health. Ms. Wei reported having no financial conflicts.

RALEIGH, N.C. – The ratio of melanoma in situ to invasive melanoma jumped 12-fold among American health professionals during a recent 3-decade period.

Just how much of this steep rise in melanoma in situ diagnoses represents a true increase in the development of in situ lesions as opposed to the product of improved screening techniques or overdiagnosis due to medicolegal pressure remains a matter for conjecture. The new analysis of melanoma trends in the Nurses' Health Study and the Health Professionals Follow-Up Study provides evidence suggesting that all three factors may be involved, according to Erin X. Wei of Massachusetts General Hospital, Boston.

Her analysis included roughly 121,000 female nurses followed prospectively in the Nurses’ Health Study since 1976 and 51,000 men followed in the Health Professionals Follow-Up Study since 1986. During the follow-up period, new cases of invasive melanoma increased dramatically, but they were far outpaced by the rise in cases of melanoma in situ, she said at the annual meeting of the Society for Investigative Dermatology.

For example, while the ratio of in situ to invasive melanoma among women was 0.09:1 in 1977, by 2002 it had reached 1:1.

Support for the notion that the rise in melanoma in situ is due in part to overdiagnosis in response to medicolegal concerns comes from the finding that the bulk of the increase involves lesions reported in this study as having Not-Otherwise-Specified pathology. Lentigo maligna cases have remained relatively flat over time, she noted.

Also, in this large patient population, as well as in studies from elsewhere around the world, the increase in melanoma in situ has not been accompanied by a shift in the pattern of invasive melanoma thickness or by a reduction in melanoma mortality, as would be expected in response to a major increase in detection of invasive melanoma precursor lesions.

But perhaps in situ melanomas are often not precursors to invasive melanoma. If they were precursors, one would expect them to be diagnosed at a younger average age than invasive melanoma. Such was not the case in this analysis. Indeed, while roughly 40% of invasive melanomas were diagnosed prior to age 60, that was true for only 20% of melanoma in situ. Nurses diagnosed with melanoma in situ were an average of 6 years older than those diagnosed with invasive melanoma; among men, the difference was 2 years.

Melanoma in situ and invasive melanomas tended to differ in their anatomic distribution. Invasive melanomas were far less likely than in situ lesions to occur on the head and neck, and much more likely to occur on the lower extremities. This suggests some in situ melanomas are indolent and do not become malignant over time, Ms. Wei continued.

In support of the existence of a true biologic increase in the incidence of melanoma in situ, Ms. Wei and her coworkers found that older individuals were two- to threefold more likely to develop their lesions on chronically sun-exposed areas than on intermittently sun-exposed areas.

An intriguing gender difference in the anatomic distribution of melanoma in situ was evident. Among men, more than 98% of all melanoma in situ were found on the upper half of the body. In women, the lesions were more evenly distributed anatomically, with 27% of in situ lesions being found on the lower extremities.

The Nurses’ Health Study and Health Professionals Follow-up Study are funded by the National Institutes of Health. Ms. Wei reported having no financial conflicts.

RALEIGH, N.C. – The ratio of melanoma in situ to invasive melanoma jumped 12-fold among American health professionals during a recent 3-decade period.

Just how much of this steep rise in melanoma in situ diagnoses represents a true increase in the development of in situ lesions as opposed to the product of improved screening techniques or overdiagnosis due to medicolegal pressure remains a matter for conjecture. The new analysis of melanoma trends in the Nurses' Health Study and the Health Professionals Follow-Up Study provides evidence suggesting that all three factors may be involved, according to Erin X. Wei of Massachusetts General Hospital, Boston.

Her analysis included roughly 121,000 female nurses followed prospectively in the Nurses’ Health Study since 1976 and 51,000 men followed in the Health Professionals Follow-Up Study since 1986. During the follow-up period, new cases of invasive melanoma increased dramatically, but they were far outpaced by the rise in cases of melanoma in situ, she said at the annual meeting of the Society for Investigative Dermatology.

For example, while the ratio of in situ to invasive melanoma among women was 0.09:1 in 1977, by 2002 it had reached 1:1.

Support for the notion that the rise in melanoma in situ is due in part to overdiagnosis in response to medicolegal concerns comes from the finding that the bulk of the increase involves lesions reported in this study as having Not-Otherwise-Specified pathology. Lentigo maligna cases have remained relatively flat over time, she noted.

Also, in this large patient population, as well as in studies from elsewhere around the world, the increase in melanoma in situ has not been accompanied by a shift in the pattern of invasive melanoma thickness or by a reduction in melanoma mortality, as would be expected in response to a major increase in detection of invasive melanoma precursor lesions.

But perhaps in situ melanomas are often not precursors to invasive melanoma. If they were precursors, one would expect them to be diagnosed at a younger average age than invasive melanoma. Such was not the case in this analysis. Indeed, while roughly 40% of invasive melanomas were diagnosed prior to age 60, that was true for only 20% of melanoma in situ. Nurses diagnosed with melanoma in situ were an average of 6 years older than those diagnosed with invasive melanoma; among men, the difference was 2 years.

Melanoma in situ and invasive melanomas tended to differ in their anatomic distribution. Invasive melanomas were far less likely than in situ lesions to occur on the head and neck, and much more likely to occur on the lower extremities. This suggests some in situ melanomas are indolent and do not become malignant over time, Ms. Wei continued.

In support of the existence of a true biologic increase in the incidence of melanoma in situ, Ms. Wei and her coworkers found that older individuals were two- to threefold more likely to develop their lesions on chronically sun-exposed areas than on intermittently sun-exposed areas.

An intriguing gender difference in the anatomic distribution of melanoma in situ was evident. Among men, more than 98% of all melanoma in situ were found on the upper half of the body. In women, the lesions were more evenly distributed anatomically, with 27% of in situ lesions being found on the lower extremities.

The Nurses’ Health Study and Health Professionals Follow-up Study are funded by the National Institutes of Health. Ms. Wei reported having no financial conflicts.

RALEIGH, N.C. – A novel small-molecule antibiotic produced by Staphylococcus epidermidis and dubbed "firmocidin" shows early promise as a potential treatment for methicillin-resistant S. aureus and other major skin pathogens, Dr. Teruaki Nakatsuji reported at the annual meeting of the Society for Investigative Dermatology.

S. epidermidis is a commensal microorganism that appears to act as "an antimicrobial shield" in healthy human skin, protecting against some of the major cutaneous bacterial pathogens. It accomplishes this by producing firmocidin, explained Dr. Nakatsuji of the University of California, San Diego.

He and his coworkers in the laboratory of Dr. Richard L. Gallo, professor of medicine and pediatrics and chief of the division of dermatology at the university, discovered the antibiotic by screening clinical isolates of S. epidermidis and identifying strains possessing pronounced antimicrobial activity. Next, they zeroed in on the antibiotic component. Using mass spectrometry and nuclear magnetic resonance spectrometry, they determined that the structure of the purified product didn’t match that of any known molecule. They named it firmocidin.

In in vitro studies, firmocidin effectively killed S. aureus, both group A and B streptococcus, and methicillin-resistant S. aureus. In these cell culture assays, firmocidin’s antimicrobial activity was stronger than that of benzoyl peroxide.

Importantly, however, firmocidin’s antibiotic activity was selective. It didn’t affect the growth of S. epidermidis or other commensal bacteria, nor did it affect human keratinocytes or sebocytes. Thus, it could potentially maintain a normal microbiome while inhibiting bacterial pathogens. Its mechanism of action involves inhibition of DNA synthesis by interfering with A-T base pair matching, he continued.

The University of California has applied for patent protection for firmocidin and has announced it is seeking business partners for its commercialization. Possibilities include its development as an antiseptic or a topical or systemic antibiotic for treatment of skin infections that does not disrupt the healthy skin microflora.

Dr. Nakatsuji reported having no financial conflicts.

RALEIGH, N.C. – A novel small-molecule antibiotic produced by Staphylococcus epidermidis and dubbed "firmocidin" shows early promise as a potential treatment for methicillin-resistant S. aureus and other major skin pathogens, Dr. Teruaki Nakatsuji reported at the annual meeting of the Society for Investigative Dermatology.

S. epidermidis is a commensal microorganism that appears to act as "an antimicrobial shield" in healthy human skin, protecting against some of the major cutaneous bacterial pathogens. It accomplishes this by producing firmocidin, explained Dr. Nakatsuji of the University of California, San Diego.

He and his coworkers in the laboratory of Dr. Richard L. Gallo, professor of medicine and pediatrics and chief of the division of dermatology at the university, discovered the antibiotic by screening clinical isolates of S. epidermidis and identifying strains possessing pronounced antimicrobial activity. Next, they zeroed in on the antibiotic component. Using mass spectrometry and nuclear magnetic resonance spectrometry, they determined that the structure of the purified product didn’t match that of any known molecule. They named it firmocidin.

In in vitro studies, firmocidin effectively killed S. aureus, both group A and B streptococcus, and methicillin-resistant S. aureus. In these cell culture assays, firmocidin’s antimicrobial activity was stronger than that of benzoyl peroxide.

Importantly, however, firmocidin’s antibiotic activity was selective. It didn’t affect the growth of S. epidermidis or other commensal bacteria, nor did it affect human keratinocytes or sebocytes. Thus, it could potentially maintain a normal microbiome while inhibiting bacterial pathogens. Its mechanism of action involves inhibition of DNA synthesis by interfering with A-T base pair matching, he continued.

The University of California has applied for patent protection for firmocidin and has announced it is seeking business partners for its commercialization. Possibilities include its development as an antiseptic or a topical or systemic antibiotic for treatment of skin infections that does not disrupt the healthy skin microflora.

Dr. Nakatsuji reported having no financial conflicts.

RALEIGH, N.C. – A novel small-molecule antibiotic produced by Staphylococcus epidermidis and dubbed "firmocidin" shows early promise as a potential treatment for methicillin-resistant S. aureus and other major skin pathogens, Dr. Teruaki Nakatsuji reported at the annual meeting of the Society for Investigative Dermatology.

S. epidermidis is a commensal microorganism that appears to act as "an antimicrobial shield" in healthy human skin, protecting against some of the major cutaneous bacterial pathogens. It accomplishes this by producing firmocidin, explained Dr. Nakatsuji of the University of California, San Diego.

He and his coworkers in the laboratory of Dr. Richard L. Gallo, professor of medicine and pediatrics and chief of the division of dermatology at the university, discovered the antibiotic by screening clinical isolates of S. epidermidis and identifying strains possessing pronounced antimicrobial activity. Next, they zeroed in on the antibiotic component. Using mass spectrometry and nuclear magnetic resonance spectrometry, they determined that the structure of the purified product didn’t match that of any known molecule. They named it firmocidin.

In in vitro studies, firmocidin effectively killed S. aureus, both group A and B streptococcus, and methicillin-resistant S. aureus. In these cell culture assays, firmocidin’s antimicrobial activity was stronger than that of benzoyl peroxide.

Importantly, however, firmocidin’s antibiotic activity was selective. It didn’t affect the growth of S. epidermidis or other commensal bacteria, nor did it affect human keratinocytes or sebocytes. Thus, it could potentially maintain a normal microbiome while inhibiting bacterial pathogens. Its mechanism of action involves inhibition of DNA synthesis by interfering with A-T base pair matching, he continued.

The University of California has applied for patent protection for firmocidin and has announced it is seeking business partners for its commercialization. Possibilities include its development as an antiseptic or a topical or systemic antibiotic for treatment of skin infections that does not disrupt the healthy skin microflora.

Dr. Nakatsuji reported having no financial conflicts.

RALEIGH, N.C. – The infra-auricular fissure present in the overwhelming majority of atopic dermatitis patients provides a simple and convenient guide to disease severity, according to the results of a prospective study.

Infra-auricular fissures are highly prevalent in atopic dermatitis patients of all ages and racial/ethnic groups and in both genders. And the form the lesion takes shows a good correlation with disease severity as measured with the Eczema Area and Severity Index (EASI) and other metrics, Dr. Gil Yosipovitch said at the annual meeting of the Society for Investigative Dermatology.

"I’m not saying this is an ideal test, but I think that it’s a very easy bedside marker that we could use in our clinics. We can’t use the EASI all the time in busy fast-track clinics," observed Dr. Yosipovitch, professor of dermatology at Wake Forest University in Winston-Salem, N.C.

He and his coinvestigators assigned an infra-auricular fissure score of 1 to atopic dermatitis patients with an infra-auricular line and a score of 2 in those with an infra-auricular line accompanied by erythema and a small fissure. Those patients with a deeper infra-auricular fissure with significant erosion got a 3.

An infra-auricular fissure was present in every one of 81 consecutive children and adults with clinician-diagnosed atopic dermatitis. Fifty-eight percent had an infra-auricular fissure score of 1, 27% had a 2, and 15% scored 3. The infra-auricular fissure score showed a strong correlation with results on the validated EASI, with a correlation coefficient of 0.6.

Moreover, among the 29 patients seen at follow-up 1-2 months later, reductions in visual analog scale itch intensity, EASI score, and Investigator Global Assessment scores in response to treatment showed a significant correlation with improvement in the infra-auricular fissure score.

Dr. Yosipovitch reported having no financial conflicts.

RALEIGH, N.C. – The infra-auricular fissure present in the overwhelming majority of atopic dermatitis patients provides a simple and convenient guide to disease severity, according to the results of a prospective study.

Infra-auricular fissures are highly prevalent in atopic dermatitis patients of all ages and racial/ethnic groups and in both genders. And the form the lesion takes shows a good correlation with disease severity as measured with the Eczema Area and Severity Index (EASI) and other metrics, Dr. Gil Yosipovitch said at the annual meeting of the Society for Investigative Dermatology.

"I’m not saying this is an ideal test, but I think that it’s a very easy bedside marker that we could use in our clinics. We can’t use the EASI all the time in busy fast-track clinics," observed Dr. Yosipovitch, professor of dermatology at Wake Forest University in Winston-Salem, N.C.

He and his coinvestigators assigned an infra-auricular fissure score of 1 to atopic dermatitis patients with an infra-auricular line and a score of 2 in those with an infra-auricular line accompanied by erythema and a small fissure. Those patients with a deeper infra-auricular fissure with significant erosion got a 3.

An infra-auricular fissure was present in every one of 81 consecutive children and adults with clinician-diagnosed atopic dermatitis. Fifty-eight percent had an infra-auricular fissure score of 1, 27% had a 2, and 15% scored 3. The infra-auricular fissure score showed a strong correlation with results on the validated EASI, with a correlation coefficient of 0.6.

Moreover, among the 29 patients seen at follow-up 1-2 months later, reductions in visual analog scale itch intensity, EASI score, and Investigator Global Assessment scores in response to treatment showed a significant correlation with improvement in the infra-auricular fissure score.

Dr. Yosipovitch reported having no financial conflicts.

RALEIGH, N.C. – The infra-auricular fissure present in the overwhelming majority of atopic dermatitis patients provides a simple and convenient guide to disease severity, according to the results of a prospective study.

Infra-auricular fissures are highly prevalent in atopic dermatitis patients of all ages and racial/ethnic groups and in both genders. And the form the lesion takes shows a good correlation with disease severity as measured with the Eczema Area and Severity Index (EASI) and other metrics, Dr. Gil Yosipovitch said at the annual meeting of the Society for Investigative Dermatology.

"I’m not saying this is an ideal test, but I think that it’s a very easy bedside marker that we could use in our clinics. We can’t use the EASI all the time in busy fast-track clinics," observed Dr. Yosipovitch, professor of dermatology at Wake Forest University in Winston-Salem, N.C.

He and his coinvestigators assigned an infra-auricular fissure score of 1 to atopic dermatitis patients with an infra-auricular line and a score of 2 in those with an infra-auricular line accompanied by erythema and a small fissure. Those patients with a deeper infra-auricular fissure with significant erosion got a 3.

An infra-auricular fissure was present in every one of 81 consecutive children and adults with clinician-diagnosed atopic dermatitis. Fifty-eight percent had an infra-auricular fissure score of 1, 27% had a 2, and 15% scored 3. The infra-auricular fissure score showed a strong correlation with results on the validated EASI, with a correlation coefficient of 0.6.

Moreover, among the 29 patients seen at follow-up 1-2 months later, reductions in visual analog scale itch intensity, EASI score, and Investigator Global Assessment scores in response to treatment showed a significant correlation with improvement in the infra-auricular fissure score.

Dr. Yosipovitch reported having no financial conflicts.

HOUSTON – Nearly one-third of obese patients who had type 2 diabetes and were randomized to an extended-release formulation of phentermine plus topiramate for 1 year achieved a rigorous composite diabetes management end point comprising greater-than-10% weight loss, an HbA_1c level lower than 6.5%, and systolic blood pressure lower than 130 mm Hg.

Moreover, almost 40% of patients who were randomized to the full dose of the drug combo achieved a less-rigorous trifecta consisting of the same blood pressure and HbA1c targets, plus a greater-than-5% weight loss, Dr. Donna H. Ryan reported at the annual meeting of the Endocrine Society.

On the basis of favorable feedback from the Food and Drug Administration, she expects the combination drug (brand name, Qnexa) will receive marketing approval before year’s end and perhaps as early as mid-July.

In late February, the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa. The FDA is expected to issue its decision by July 17.

The approved indication will be for medical weight loss in the treatment of obesity in patients with either a body mass index of at least 30 kg/m², or a BMI of 27 plus a comorbid condition, such as type 2 diabetes, according to Dr. Ryan of the Pennington Biomedical Research Center in Baton Rouge, La.

If approved, Qnexa would join lorcaserin (Belviq), which was approved by the FDA in late June and which also is indicated for patients with either a BMI of at least 30, or a BMI of at least 27 plus weight-related comorbidities.

More than 25 million Americans have type 2 diabetes, and most of them are obese.

Because both the FDA and Vivus Inc. (Qnexa’s developer) want to avoid the widespread abuse that often has been a problem with diet medications, the drug will be subject to a risk-management program. It will be available only through certified mail-order pharmacies that will collect patient data.

"This won’t be something you can get over the Internet. Patients won’t be able to go to a doc-in-a-box and say, ‘I want a diet drug; give me a prescription for this drug I read about in the newspaper.’ It won’t be like that," she said.

Dr. Ryan presented a secondary analysis from the randomized, double-blind, phase III CONQUER trial that involved roughly 2,500 obese patients (Lancet 2011;377:1341-52).

Her new substudy focused on the 388 CONQUER participants with type 2 diabetes. Like all participants in CONQUER, the diabetic patients were placed on a well-known, structured, lifestyle/behavioral modification program known as the LEARN (lifestyle, exercise, attitudes, relationships, nutrition) program for weight management. In addition, they were randomized to phentermine 7.5 mg/topiramate 46 mg, to phentermine 15 mg/topiramate 92 mg, or to placebo once daily. The subjects had relatively well-controlled diabetes and were on metformin as their sole antidiabetic medication at baseline.

At 56 weeks, the composite goal of a greater-than-5% weight loss from baseline, an HbA_1c level lower than 6.5%, and a systolic blood pressure lower than 130 mm Hg was met by 12% of patients on lifestyle modification plus placebo, by 27% of those on the lifestyle program and the lower dose, and by 39% of those on the full dose. The tougher goal, which involved a greater-than-10% weight loss, was achieved in 4% of controls, 14% on the lower dose, and 31% on the full dose, which suggests that the drug plus lifestyle modification was roughly eightfold more effective than lifestyle modification alone.

The mean weight loss from baseline was 2% in controls, 7% in patients on the lower dose, and 9% in those on full-dose therapy.

To reach the composite goals, 12% of control subjects required a net increase in antidiabetic medications, as did 2% of those on the low dose and 0.6% of those on the full dose.

Both phentermine and topiramate have been on the market as individual drugs for many years, and their side effects in the CONQUER diabetic subgroup were the familiar ones associated with those agents. Dry mouth and paresthesia each occurred in about 8% of patients on the lower dose, and constipation occurred in 15%. Because the side effects are dose related, it’s quite likely that phentermine 7.5 mg/topiramate 46 mg will be the recommended starting dose, according to Dr. Ryan.

Topiramate is a known teratogen with a risk of four or five cases of cleft palate per 1,000 exposures during pregnancy. For this reason, the combination drug will be a category X drug.

In an interview, Dr. Ryan said that she could see physicians setting up contracts with their patients to take the drug for at least a year, then stopping it in order to see if lifestyle modification efforts enable them to avoid weight regain. If the pounds start piling up, they’ll restart the drug.

Dr. Ryan reported serving as a scientific advisor to Vivus but holds no equity interest in the company.

HOUSTON – Nearly one-third of obese patients who had type 2 diabetes and were randomized to an extended-release formulation of phentermine plus topiramate for 1 year achieved a rigorous composite diabetes management end point comprising greater-than-10% weight loss, an HbA_1c level lower than 6.5%, and systolic blood pressure lower than 130 mm Hg.

Moreover, almost 40% of patients who were randomized to the full dose of the drug combo achieved a less-rigorous trifecta consisting of the same blood pressure and HbA1c targets, plus a greater-than-5% weight loss, Dr. Donna H. Ryan reported at the annual meeting of the Endocrine Society.

On the basis of favorable feedback from the Food and Drug Administration, she expects the combination drug (brand name, Qnexa) will receive marketing approval before year’s end and perhaps as early as mid-July.

In late February, the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa. The FDA is expected to issue its decision by July 17.

The approved indication will be for medical weight loss in the treatment of obesity in patients with either a body mass index of at least 30 kg/m², or a BMI of 27 plus a comorbid condition, such as type 2 diabetes, according to Dr. Ryan of the Pennington Biomedical Research Center in Baton Rouge, La.

If approved, Qnexa would join lorcaserin (Belviq), which was approved by the FDA in late June and which also is indicated for patients with either a BMI of at least 30, or a BMI of at least 27 plus weight-related comorbidities.

More than 25 million Americans have type 2 diabetes, and most of them are obese.

Because both the FDA and Vivus Inc. (Qnexa’s developer) want to avoid the widespread abuse that often has been a problem with diet medications, the drug will be subject to a risk-management program. It will be available only through certified mail-order pharmacies that will collect patient data.

"This won’t be something you can get over the Internet. Patients won’t be able to go to a doc-in-a-box and say, ‘I want a diet drug; give me a prescription for this drug I read about in the newspaper.’ It won’t be like that," she said.

Dr. Ryan presented a secondary analysis from the randomized, double-blind, phase III CONQUER trial that involved roughly 2,500 obese patients (Lancet 2011;377:1341-52).

Her new substudy focused on the 388 CONQUER participants with type 2 diabetes. Like all participants in CONQUER, the diabetic patients were placed on a well-known, structured, lifestyle/behavioral modification program known as the LEARN (lifestyle, exercise, attitudes, relationships, nutrition) program for weight management. In addition, they were randomized to phentermine 7.5 mg/topiramate 46 mg, to phentermine 15 mg/topiramate 92 mg, or to placebo once daily. The subjects had relatively well-controlled diabetes and were on metformin as their sole antidiabetic medication at baseline.

At 56 weeks, the composite goal of a greater-than-5% weight loss from baseline, an HbA_1c level lower than 6.5%, and a systolic blood pressure lower than 130 mm Hg was met by 12% of patients on lifestyle modification plus placebo, by 27% of those on the lifestyle program and the lower dose, and by 39% of those on the full dose. The tougher goal, which involved a greater-than-10% weight loss, was achieved in 4% of controls, 14% on the lower dose, and 31% on the full dose, which suggests that the drug plus lifestyle modification was roughly eightfold more effective than lifestyle modification alone.

The mean weight loss from baseline was 2% in controls, 7% in patients on the lower dose, and 9% in those on full-dose therapy.

To reach the composite goals, 12% of control subjects required a net increase in antidiabetic medications, as did 2% of those on the low dose and 0.6% of those on the full dose.

Both phentermine and topiramate have been on the market as individual drugs for many years, and their side effects in the CONQUER diabetic subgroup were the familiar ones associated with those agents. Dry mouth and paresthesia each occurred in about 8% of patients on the lower dose, and constipation occurred in 15%. Because the side effects are dose related, it’s quite likely that phentermine 7.5 mg/topiramate 46 mg will be the recommended starting dose, according to Dr. Ryan.

Topiramate is a known teratogen with a risk of four or five cases of cleft palate per 1,000 exposures during pregnancy. For this reason, the combination drug will be a category X drug.

In an interview, Dr. Ryan said that she could see physicians setting up contracts with their patients to take the drug for at least a year, then stopping it in order to see if lifestyle modification efforts enable them to avoid weight regain. If the pounds start piling up, they’ll restart the drug.

Dr. Ryan reported serving as a scientific advisor to Vivus but holds no equity interest in the company.

HOUSTON – Nearly one-third of obese patients who had type 2 diabetes and were randomized to an extended-release formulation of phentermine plus topiramate for 1 year achieved a rigorous composite diabetes management end point comprising greater-than-10% weight loss, an HbA_1c level lower than 6.5%, and systolic blood pressure lower than 130 mm Hg.

Moreover, almost 40% of patients who were randomized to the full dose of the drug combo achieved a less-rigorous trifecta consisting of the same blood pressure and HbA1c targets, plus a greater-than-5% weight loss, Dr. Donna H. Ryan reported at the annual meeting of the Endocrine Society.

On the basis of favorable feedback from the Food and Drug Administration, she expects the combination drug (brand name, Qnexa) will receive marketing approval before year’s end and perhaps as early as mid-July.

In late February, the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa. The FDA is expected to issue its decision by July 17.

The approved indication will be for medical weight loss in the treatment of obesity in patients with either a body mass index of at least 30 kg/m², or a BMI of 27 plus a comorbid condition, such as type 2 diabetes, according to Dr. Ryan of the Pennington Biomedical Research Center in Baton Rouge, La.

If approved, Qnexa would join lorcaserin (Belviq), which was approved by the FDA in late June and which also is indicated for patients with either a BMI of at least 30, or a BMI of at least 27 plus weight-related comorbidities.

More than 25 million Americans have type 2 diabetes, and most of them are obese.

Because both the FDA and Vivus Inc. (Qnexa’s developer) want to avoid the widespread abuse that often has been a problem with diet medications, the drug will be subject to a risk-management program. It will be available only through certified mail-order pharmacies that will collect patient data.

"This won’t be something you can get over the Internet. Patients won’t be able to go to a doc-in-a-box and say, ‘I want a diet drug; give me a prescription for this drug I read about in the newspaper.’ It won’t be like that," she said.

Dr. Ryan presented a secondary analysis from the randomized, double-blind, phase III CONQUER trial that involved roughly 2,500 obese patients (Lancet 2011;377:1341-52).

Her new substudy focused on the 388 CONQUER participants with type 2 diabetes. Like all participants in CONQUER, the diabetic patients were placed on a well-known, structured, lifestyle/behavioral modification program known as the LEARN (lifestyle, exercise, attitudes, relationships, nutrition) program for weight management. In addition, they were randomized to phentermine 7.5 mg/topiramate 46 mg, to phentermine 15 mg/topiramate 92 mg, or to placebo once daily. The subjects had relatively well-controlled diabetes and were on metformin as their sole antidiabetic medication at baseline.

At 56 weeks, the composite goal of a greater-than-5% weight loss from baseline, an HbA_1c level lower than 6.5%, and a systolic blood pressure lower than 130 mm Hg was met by 12% of patients on lifestyle modification plus placebo, by 27% of those on the lifestyle program and the lower dose, and by 39% of those on the full dose. The tougher goal, which involved a greater-than-10% weight loss, was achieved in 4% of controls, 14% on the lower dose, and 31% on the full dose, which suggests that the drug plus lifestyle modification was roughly eightfold more effective than lifestyle modification alone.

The mean weight loss from baseline was 2% in controls, 7% in patients on the lower dose, and 9% in those on full-dose therapy.

To reach the composite goals, 12% of control subjects required a net increase in antidiabetic medications, as did 2% of those on the low dose and 0.6% of those on the full dose.

Both phentermine and topiramate have been on the market as individual drugs for many years, and their side effects in the CONQUER diabetic subgroup were the familiar ones associated with those agents. Dry mouth and paresthesia each occurred in about 8% of patients on the lower dose, and constipation occurred in 15%. Because the side effects are dose related, it’s quite likely that phentermine 7.5 mg/topiramate 46 mg will be the recommended starting dose, according to Dr. Ryan.

Topiramate is a known teratogen with a risk of four or five cases of cleft palate per 1,000 exposures during pregnancy. For this reason, the combination drug will be a category X drug.

In an interview, Dr. Ryan said that she could see physicians setting up contracts with their patients to take the drug for at least a year, then stopping it in order to see if lifestyle modification efforts enable them to avoid weight regain. If the pounds start piling up, they’ll restart the drug.

Dr. Ryan reported serving as a scientific advisor to Vivus but holds no equity interest in the company.