Kari Oakes

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – A small study of cloth diaper–wearing toddlers with unusual vesiculobullous and erosive lesions found that the rashes fully resolved with aggressive barrier cream application and a switch to disposable diapers.

The four patients had previously received aggressive work-ups, including biopsy in some cases; all had received systemic antibiotics. Katya L. Harfmann, MD, a pediatric dermatologist at Nationwide Children’s Hospital in Columbus, Ohio, was the lead author in a poster presentation at the annual meeting of the Society for Pediatric Dermatology.

The toddlers, aged 17 months to 2 years, had diaper dermatitis of several weeks’ to several months’ duration, with a presentation of vesicles, bullae, and erosions. All of the children had been placed in cloth diapers since birth. The patients, three of them male, had undergone work-ups that included bacterial culture for three patients, herpes simplex virus (HSV) polymerase chain reaction (PCR) testing for three patients, and blood work for two patients. HSV cultures and viral cultures were each performed on one patient. With the exception of one bacterial culture returning methicillin-sensitive Staphylococcus aureus (MSSA), all results were negative.

Two patients underwent biopsies. One biopsy was reported as “spongiform dermatitis,” while the other was read as a “nonspecific ulcer.”

A variety of treatments had been tried for the children. All of the children had received systemic antibiotics; two received systemic antivirals as well. Two patients each received topical steroids and topical antibacterials, and one patient also received topical dapsone. Many treatments were given “in repetitive courses, without improvement in the lesions,” wrote Dr. Harfmann and her coauthor.

The families were advised to switch to exclusive use of disposable diapers and to begin frequent use of a zinc oxide–based thick diaper paste. For all patients, the diaper dermatitis completely resolved within as little as 2 weeks.

The medical literature documents an increased risk of diaper dermatitis with cloth diaper use. “Despite this knowledge in the medical community, nearly half of cloth diaper–using parents select cloth diapers with the assumption that diaper rash is less frequent with their usage,” the researchers noted.

They pointed out that bullae in the diaper region are often thought to be associated with such infectious conditions as impetigo and herpes simplex infection, and can also be associated with immunobullous disorders. Diaper changes are less frequent in older children, though, giving the opportunity for prolonged contact with the irritating chemicals in feces and urine. This prolonged contact, exacerbated by the moister environment of a cloth diaper, may account for the unusual, severe presentation seen in these cases.

Also, the three boys had vesicular lesions on their testicles and penis. “It is possible that the thinner skin in these areas has a lower irritation threshold or that the redundancy of skin often seen on the penile shaft leads to trapping of irritants with extended diaper use,” they wrote.

“An empiric trial of disposable diapers exclusively with aggressive barrier cream application for several weeks may eliminate the need for more invasive procedures and laboratory tests,” wrote Dr. Harfmann and her coauthor.

They reported no conflicts of interest.

[email protected]

On Twitter @karioakes

A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.

Courtesy of the National Institute of Allergy and Infectious Diseases

The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”

The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.

The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.

Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.

Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.

The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.

Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.

However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”

Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”

The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.

Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.

[email protected]

On Twitter @karioakes

A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.

Courtesy of the National Institute of Allergy and Infectious Diseases

The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”

The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.

The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.

Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.

Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.

The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.

Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.

However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”

Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”

The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.

Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.

[email protected]

On Twitter @karioakes

A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.

Courtesy of the National Institute of Allergy and Infectious Diseases

The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”

The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.

The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.

Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.

Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.

The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.

Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.

However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”

Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”

The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.

Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.

[email protected]

On Twitter @karioakes

SCOTTSDALE, ARIZ. – A sublingual formulation of cyclobenzaprine taken at bedtime was significantly better than placebo at reducing symptoms of military-related posttraumatic stress disorder, and study participants taking cyclobenzaprine also reported better sleep, a study showed.

After 12 weeks of nightly use at bedtime, 5.6 mg of sublingual cyclobenzaprine (CBP) resulted in a significant reduction on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), compared with placebo. Under several different analytic and data imputation methods, CAPS-5 values improved by 20.2 to 22.6 points from baseline for the 5.6-mg group, compared with reductions of 17.4 to 20.6 for the placebo group (P value range, 0.038-0.016). Improvement in the CAPS-5 was the study’s primary efficacy outcome measure.

Patients also saw significantly improved global symptoms, as assessed by the Clinician Global Impression – Improvement scale (CGI-I; 63.3% responders cyclobenzaprine versus 44.6% placebo, P = 0.041).

Significant reductions in hyperarousal (P less than 0.05) and exaggerated startle (P =0.015) symptoms also were seen in the 5.6-mg cyclobenzaprine group, and those participants also had significantly less symptom-related disruption in work/school, and in social/leisure activities, as measured by those domains on the Sheehan Disability Scale (for both, P less than 0.050).

Gregory M. Sullivan, MD, chief medical officer of Tonix Pharmaceuticals, presented these findings from AtEase, a randomized, placebo-controlled, double-blind study of sublingual cyclobenzaprine for military PTSD, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Drug Clinical Evaluation Unit meeting.

The phase II safety, efficacy, and dose-ranging study of 245 patients (231 in the modified intent-to-treat population, and 237 in the safety population) also compared 2.8- and 5.6-mg sublingual doses. At the end of the 12-week study period, those on the lower dose did not experience significantly improved sleep or PTSD symptoms.

The AtEase participants were current or former servicemembers with PTSD. Ninety-three percent of the patients were male and had been deployed an average of 2.3 times. The index trauma occurred a mean of 7 years ago. Demographic distribution was representative of the U.S. military, according to Dr. Sullivan. The mean CAPS-5 and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were similar across treatment arms. The mean CAPS-5 score for participants in the study was 39.5 representing “severe” PTSD. “These people are quite ill,” said Seth Lederman, MD, Tonix CEO, in an interview.

Oral symptoms were the most frequent side effects reported in the safety analysis. Of those taking the 2.8-mg cyclobenzaprine dose, 38.7% (36/93) experienced oral hypoesthesia, as did 36% (18/50) of the 5.6-mg dosing group. This compared with 2.1% (2/94) of the placebo group. Somnolence was noted by 11.8% (11/93) of the lower dose group, by 16% (8/50) of the higher dose group, and by 6.4% (6/94) of the placebo group. No participants discontinued the study because of adverse events.

Military traumatic brain injury may be different from most civilian TBI, said Dr. Lederman, because of both the intensity and duration of the events that precipitated the condition. Most military-related trauma stems from combat, and most patients with military-related trauma are men; in the civilian population, PTSD patients are predominantly women. “Especially in today’s military, servicemembers are deploying multiple times,” he noted. “Everyone has their breaking point.”

Effective medical treatments for military PTSD are lacking, said Dr. Sullivan. One multicenter trial found that sertraline not effective for PTSD in military veterans (J Clin Psychiatry. 2007 May;68[5]:711-20), and selective serotonin reuptake inhibitors are associated with sexual dysfunction and insomnia for some patients.

Cyclobenzaprine is thought to interact with several receptors thought to be important for sleep, including 5-HT2A, alpha-1 adrenergic, and H1 histamine receptors.

Problems with sleep for individuals with PTSD may include nightmares, as well as sleep disturbances associated with the hyperarousal that characterizes the disorder. Sleep disruption may contribute to “attenuated extinction consolidation, or a delay in the processing of emotionally charged memories,” Dr. Sullivan said. Sleep disturbances in those with PTSD also are associated with depression, substance use disorders, and suicidal behavior.

“Processing memories is an essential part of learning and extinction,” Dr. Lederman said. “We saw startle improve” in the clinical trial of sublingual cyclobenzaprine, an indication of diminished hyperarousal, he said.

The sublingual formulation, said Dr. Lederman, avoids first-pass metabolism of cyclobenzaprine, which converts large amounts of the dose to norcyclobenzaprine. This metabolite has a much longer half-life than cyclobenzaprine and is responsible, in large part, for the persistent grogginess many patients report when taking the oral formulation of the medication. Previous work showed that the exposure ratio for cyclobenzaprine/norcyclobenzaprine for oral immediate-release cyclobenzaprine was 1.2, compared with 1.9 for sublingual cyclobenzaprine

“With the sublingual formulation, we hope to achieve a true ‘on-off’ effect, really helping sleep quality and improving sleep architecture,” Dr. Lederman said.

“Early effects on sleep and hyperarousal are consistent with the mechanistic hypothesis that TNX-102 SL’s primary actions on sleep architecture and autonomic balance underlie the observed PTSD treatment effect,” wrote Dr. Sullivan. The later reduction in exaggerated startle is consistent with the memory consolidation hypothesis, he said.

Sublingual cyclobenzaprine also is being trialed for fibromyalgia, another condition where significant sleep disruption can be a prominent symptom. Next steps for military PTSD include a larger clinical trial that plans to enroll 450 patients, said Dr. Lederman.

Dr. Lederman and Dr. Sullivan are both employed by Tonix Pharmaceuticals, which was the sponsor of the AtEase study.

[email protected]

On Twitter @karioakes

SCOTTSDALE, ARIZ. – A sublingual formulation of cyclobenzaprine taken at bedtime was significantly better than placebo at reducing symptoms of military-related posttraumatic stress disorder, and study participants taking cyclobenzaprine also reported better sleep, a study showed.

After 12 weeks of nightly use at bedtime, 5.6 mg of sublingual cyclobenzaprine (CBP) resulted in a significant reduction on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), compared with placebo. Under several different analytic and data imputation methods, CAPS-5 values improved by 20.2 to 22.6 points from baseline for the 5.6-mg group, compared with reductions of 17.4 to 20.6 for the placebo group (P value range, 0.038-0.016). Improvement in the CAPS-5 was the study’s primary efficacy outcome measure.

Patients also saw significantly improved global symptoms, as assessed by the Clinician Global Impression – Improvement scale (CGI-I; 63.3% responders cyclobenzaprine versus 44.6% placebo, P = 0.041).

Significant reductions in hyperarousal (P less than 0.05) and exaggerated startle (P =0.015) symptoms also were seen in the 5.6-mg cyclobenzaprine group, and those participants also had significantly less symptom-related disruption in work/school, and in social/leisure activities, as measured by those domains on the Sheehan Disability Scale (for both, P less than 0.050).

Gregory M. Sullivan, MD, chief medical officer of Tonix Pharmaceuticals, presented these findings from AtEase, a randomized, placebo-controlled, double-blind study of sublingual cyclobenzaprine for military PTSD, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Drug Clinical Evaluation Unit meeting.

The phase II safety, efficacy, and dose-ranging study of 245 patients (231 in the modified intent-to-treat population, and 237 in the safety population) also compared 2.8- and 5.6-mg sublingual doses. At the end of the 12-week study period, those on the lower dose did not experience significantly improved sleep or PTSD symptoms.

The AtEase participants were current or former servicemembers with PTSD. Ninety-three percent of the patients were male and had been deployed an average of 2.3 times. The index trauma occurred a mean of 7 years ago. Demographic distribution was representative of the U.S. military, according to Dr. Sullivan. The mean CAPS-5 and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were similar across treatment arms. The mean CAPS-5 score for participants in the study was 39.5 representing “severe” PTSD. “These people are quite ill,” said Seth Lederman, MD, Tonix CEO, in an interview.

Oral symptoms were the most frequent side effects reported in the safety analysis. Of those taking the 2.8-mg cyclobenzaprine dose, 38.7% (36/93) experienced oral hypoesthesia, as did 36% (18/50) of the 5.6-mg dosing group. This compared with 2.1% (2/94) of the placebo group. Somnolence was noted by 11.8% (11/93) of the lower dose group, by 16% (8/50) of the higher dose group, and by 6.4% (6/94) of the placebo group. No participants discontinued the study because of adverse events.

Military traumatic brain injury may be different from most civilian TBI, said Dr. Lederman, because of both the intensity and duration of the events that precipitated the condition. Most military-related trauma stems from combat, and most patients with military-related trauma are men; in the civilian population, PTSD patients are predominantly women. “Especially in today’s military, servicemembers are deploying multiple times,” he noted. “Everyone has their breaking point.”

Effective medical treatments for military PTSD are lacking, said Dr. Sullivan. One multicenter trial found that sertraline not effective for PTSD in military veterans (J Clin Psychiatry. 2007 May;68[5]:711-20), and selective serotonin reuptake inhibitors are associated with sexual dysfunction and insomnia for some patients.

Cyclobenzaprine is thought to interact with several receptors thought to be important for sleep, including 5-HT2A, alpha-1 adrenergic, and H1 histamine receptors.

Problems with sleep for individuals with PTSD may include nightmares, as well as sleep disturbances associated with the hyperarousal that characterizes the disorder. Sleep disruption may contribute to “attenuated extinction consolidation, or a delay in the processing of emotionally charged memories,” Dr. Sullivan said. Sleep disturbances in those with PTSD also are associated with depression, substance use disorders, and suicidal behavior.

“Processing memories is an essential part of learning and extinction,” Dr. Lederman said. “We saw startle improve” in the clinical trial of sublingual cyclobenzaprine, an indication of diminished hyperarousal, he said.

The sublingual formulation, said Dr. Lederman, avoids first-pass metabolism of cyclobenzaprine, which converts large amounts of the dose to norcyclobenzaprine. This metabolite has a much longer half-life than cyclobenzaprine and is responsible, in large part, for the persistent grogginess many patients report when taking the oral formulation of the medication. Previous work showed that the exposure ratio for cyclobenzaprine/norcyclobenzaprine for oral immediate-release cyclobenzaprine was 1.2, compared with 1.9 for sublingual cyclobenzaprine

“With the sublingual formulation, we hope to achieve a true ‘on-off’ effect, really helping sleep quality and improving sleep architecture,” Dr. Lederman said.

“Early effects on sleep and hyperarousal are consistent with the mechanistic hypothesis that TNX-102 SL’s primary actions on sleep architecture and autonomic balance underlie the observed PTSD treatment effect,” wrote Dr. Sullivan. The later reduction in exaggerated startle is consistent with the memory consolidation hypothesis, he said.

Sublingual cyclobenzaprine also is being trialed for fibromyalgia, another condition where significant sleep disruption can be a prominent symptom. Next steps for military PTSD include a larger clinical trial that plans to enroll 450 patients, said Dr. Lederman.

Dr. Lederman and Dr. Sullivan are both employed by Tonix Pharmaceuticals, which was the sponsor of the AtEase study.

[email protected]

On Twitter @karioakes

SCOTTSDALE, ARIZ. – A sublingual formulation of cyclobenzaprine taken at bedtime was significantly better than placebo at reducing symptoms of military-related posttraumatic stress disorder, and study participants taking cyclobenzaprine also reported better sleep, a study showed.

After 12 weeks of nightly use at bedtime, 5.6 mg of sublingual cyclobenzaprine (CBP) resulted in a significant reduction on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), compared with placebo. Under several different analytic and data imputation methods, CAPS-5 values improved by 20.2 to 22.6 points from baseline for the 5.6-mg group, compared with reductions of 17.4 to 20.6 for the placebo group (P value range, 0.038-0.016). Improvement in the CAPS-5 was the study’s primary efficacy outcome measure.

Patients also saw significantly improved global symptoms, as assessed by the Clinician Global Impression – Improvement scale (CGI-I; 63.3% responders cyclobenzaprine versus 44.6% placebo, P = 0.041).

Significant reductions in hyperarousal (P less than 0.05) and exaggerated startle (P =0.015) symptoms also were seen in the 5.6-mg cyclobenzaprine group, and those participants also had significantly less symptom-related disruption in work/school, and in social/leisure activities, as measured by those domains on the Sheehan Disability Scale (for both, P less than 0.050).

Gregory M. Sullivan, MD, chief medical officer of Tonix Pharmaceuticals, presented these findings from AtEase, a randomized, placebo-controlled, double-blind study of sublingual cyclobenzaprine for military PTSD, at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Drug Clinical Evaluation Unit meeting.

The phase II safety, efficacy, and dose-ranging study of 245 patients (231 in the modified intent-to-treat population, and 237 in the safety population) also compared 2.8- and 5.6-mg sublingual doses. At the end of the 12-week study period, those on the lower dose did not experience significantly improved sleep or PTSD symptoms.

The AtEase participants were current or former servicemembers with PTSD. Ninety-three percent of the patients were male and had been deployed an average of 2.3 times. The index trauma occurred a mean of 7 years ago. Demographic distribution was representative of the U.S. military, according to Dr. Sullivan. The mean CAPS-5 and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were similar across treatment arms. The mean CAPS-5 score for participants in the study was 39.5 representing “severe” PTSD. “These people are quite ill,” said Seth Lederman, MD, Tonix CEO, in an interview.

Oral symptoms were the most frequent side effects reported in the safety analysis. Of those taking the 2.8-mg cyclobenzaprine dose, 38.7% (36/93) experienced oral hypoesthesia, as did 36% (18/50) of the 5.6-mg dosing group. This compared with 2.1% (2/94) of the placebo group. Somnolence was noted by 11.8% (11/93) of the lower dose group, by 16% (8/50) of the higher dose group, and by 6.4% (6/94) of the placebo group. No participants discontinued the study because of adverse events.

Military traumatic brain injury may be different from most civilian TBI, said Dr. Lederman, because of both the intensity and duration of the events that precipitated the condition. Most military-related trauma stems from combat, and most patients with military-related trauma are men; in the civilian population, PTSD patients are predominantly women. “Especially in today’s military, servicemembers are deploying multiple times,” he noted. “Everyone has their breaking point.”

Effective medical treatments for military PTSD are lacking, said Dr. Sullivan. One multicenter trial found that sertraline not effective for PTSD in military veterans (J Clin Psychiatry. 2007 May;68[5]:711-20), and selective serotonin reuptake inhibitors are associated with sexual dysfunction and insomnia for some patients.

Cyclobenzaprine is thought to interact with several receptors thought to be important for sleep, including 5-HT2A, alpha-1 adrenergic, and H1 histamine receptors.

Problems with sleep for individuals with PTSD may include nightmares, as well as sleep disturbances associated with the hyperarousal that characterizes the disorder. Sleep disruption may contribute to “attenuated extinction consolidation, or a delay in the processing of emotionally charged memories,” Dr. Sullivan said. Sleep disturbances in those with PTSD also are associated with depression, substance use disorders, and suicidal behavior.

“Processing memories is an essential part of learning and extinction,” Dr. Lederman said. “We saw startle improve” in the clinical trial of sublingual cyclobenzaprine, an indication of diminished hyperarousal, he said.

The sublingual formulation, said Dr. Lederman, avoids first-pass metabolism of cyclobenzaprine, which converts large amounts of the dose to norcyclobenzaprine. This metabolite has a much longer half-life than cyclobenzaprine and is responsible, in large part, for the persistent grogginess many patients report when taking the oral formulation of the medication. Previous work showed that the exposure ratio for cyclobenzaprine/norcyclobenzaprine for oral immediate-release cyclobenzaprine was 1.2, compared with 1.9 for sublingual cyclobenzaprine

“With the sublingual formulation, we hope to achieve a true ‘on-off’ effect, really helping sleep quality and improving sleep architecture,” Dr. Lederman said.

“Early effects on sleep and hyperarousal are consistent with the mechanistic hypothesis that TNX-102 SL’s primary actions on sleep architecture and autonomic balance underlie the observed PTSD treatment effect,” wrote Dr. Sullivan. The later reduction in exaggerated startle is consistent with the memory consolidation hypothesis, he said.

Sublingual cyclobenzaprine also is being trialed for fibromyalgia, another condition where significant sleep disruption can be a prominent symptom. Next steps for military PTSD include a larger clinical trial that plans to enroll 450 patients, said Dr. Lederman.

Dr. Lederman and Dr. Sullivan are both employed by Tonix Pharmaceuticals, which was the sponsor of the AtEase study.

[email protected]

On Twitter @karioakes

BALTIMORE – Motivational interviewing (MI) was well accepted by providers as part of a communication tool kit to improve human papillomavirus vaccine uptake, according to results of an eight-site study.

Overall, most of the 107 medical providers who participated in the cluster-randomized trial found MI to be a “somewhat useful” (47%) or “very useful” (31%) tactic to use when discussing human papillomavirus (HPV) vaccination with parents of adolescents. The overall amount of time that providers spent discussing vaccinations actually decreased after implementing MI; at the same time, providers felt that they had more power to influence parental decision-making when using MI techniques.

©Cathy Yeulet/Thinkstock

“Primary care providers given the Physician Communication Toolkit used MI frequently, and this use was generally sustained over time,” said lead author Amanda Dempsey, MD, who presented the findings during a poster symposium at the annual meeting of the Pediatric Academic Societies.

Motivational interviewing, an open-ended, nonjudgmental listening and communication style, was taught to providers in one 30-minute webinar and two 1-hour in-person role-playing sessions. Participants were able to practice using MI both in circumstances where parents were accepting of vaccination, and with vaccine-hesitant families.

Participating providers were surveyed pretraining and at 4, 7, and 10 months after the training to assess their practices in the preceding month. The two primary outcome measures assessed, and compared from baseline, were the estimated time spent discussing HPV vaccination with both vaccine-hesitant and nonhesitant families, and the providers’ perceived abilities to influence decisions about HPV. Dr. Dempsey and her colleagues also asked whether practitioners were actually using MI techniques with vaccine-hesitant parents, and whether they found the techniques useful in HPV vaccination discussions.

Dr. Dempsey, associate professor of pediatrics at Children’s Hospital Colorado in Aurora, said that uptake of MI was initially high and remained so. Three months after the intervention, 85% of providers reported they were using MI; at 9 months after the intervention, the figure was 72%.

Previous research has shown that providers generally do not communicate strong recommendations about HPV vaccination. “Providers often feel the parents will argue with them about it, and sometimes don’t even bring it up,” Dr. Dempsey said in an interview. “Anecdotally, providers found MI a useful way to frame the conversation, and they found it less confrontational.”

Overall, about three-quarters of providers responding to the sequential surveys were physicians, another 15%-20% were physician assistants, and the remainder were nurse practitioners. About one in four respondents were male. The pediatric and family medicine practices were approximately evenly divided between public and private clinics.

Although participation in the training and the subsequent surveys was voluntary, uptake was fairly high at participating clinics. The training was offered for 25 MOC (maintenance of certification) part 4 credits, which probably helped participation rates, said Dr. Dempsey.

The small sample size of the study, said Dr. Dempsey, limits the generalizability of the findings. However, the eight sites chosen represented a wide range of socioeconomic and cultural demographics in the patients served. Also, self-report of MI use may be subject to some bias. Finally, because this was a naturalistic study that allowed providers full discretion in using the various components of the Physician Communication Toolkit, it was not possible to perform a completely independent analysis of the effects of using MI apart from the other toolkit components.

“Use of MI did not appear to lengthen the time of clinical visits, and in some cases may actually shorten them,” said Dr. Dempsey. In addition to analyzing whether MI and other components of the toolkit increased HPV vaccine uptake rates, Dr. Dempsey and her colleagues also plan to explore whether MI would be an effective approach to use when discussing immunizations with parents of infants and younger children.

The study was funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention, with survey administration supported by the National Institutes of Health. Dr. Dempsey reported no conflicts of interest.

[email protected]

On Twitter @karioakes

BALTIMORE – Motivational interviewing (MI) was well accepted by providers as part of a communication tool kit to improve human papillomavirus vaccine uptake, according to results of an eight-site study.

Overall, most of the 107 medical providers who participated in the cluster-randomized trial found MI to be a “somewhat useful” (47%) or “very useful” (31%) tactic to use when discussing human papillomavirus (HPV) vaccination with parents of adolescents. The overall amount of time that providers spent discussing vaccinations actually decreased after implementing MI; at the same time, providers felt that they had more power to influence parental decision-making when using MI techniques.

©Cathy Yeulet/Thinkstock

“Primary care providers given the Physician Communication Toolkit used MI frequently, and this use was generally sustained over time,” said lead author Amanda Dempsey, MD, who presented the findings during a poster symposium at the annual meeting of the Pediatric Academic Societies.

Motivational interviewing, an open-ended, nonjudgmental listening and communication style, was taught to providers in one 30-minute webinar and two 1-hour in-person role-playing sessions. Participants were able to practice using MI both in circumstances where parents were accepting of vaccination, and with vaccine-hesitant families.

Participating providers were surveyed pretraining and at 4, 7, and 10 months after the training to assess their practices in the preceding month. The two primary outcome measures assessed, and compared from baseline, were the estimated time spent discussing HPV vaccination with both vaccine-hesitant and nonhesitant families, and the providers’ perceived abilities to influence decisions about HPV. Dr. Dempsey and her colleagues also asked whether practitioners were actually using MI techniques with vaccine-hesitant parents, and whether they found the techniques useful in HPV vaccination discussions.

Dr. Dempsey, associate professor of pediatrics at Children’s Hospital Colorado in Aurora, said that uptake of MI was initially high and remained so. Three months after the intervention, 85% of providers reported they were using MI; at 9 months after the intervention, the figure was 72%.

Previous research has shown that providers generally do not communicate strong recommendations about HPV vaccination. “Providers often feel the parents will argue with them about it, and sometimes don’t even bring it up,” Dr. Dempsey said in an interview. “Anecdotally, providers found MI a useful way to frame the conversation, and they found it less confrontational.”

Overall, about three-quarters of providers responding to the sequential surveys were physicians, another 15%-20% were physician assistants, and the remainder were nurse practitioners. About one in four respondents were male. The pediatric and family medicine practices were approximately evenly divided between public and private clinics.

Although participation in the training and the subsequent surveys was voluntary, uptake was fairly high at participating clinics. The training was offered for 25 MOC (maintenance of certification) part 4 credits, which probably helped participation rates, said Dr. Dempsey.

The small sample size of the study, said Dr. Dempsey, limits the generalizability of the findings. However, the eight sites chosen represented a wide range of socioeconomic and cultural demographics in the patients served. Also, self-report of MI use may be subject to some bias. Finally, because this was a naturalistic study that allowed providers full discretion in using the various components of the Physician Communication Toolkit, it was not possible to perform a completely independent analysis of the effects of using MI apart from the other toolkit components.

“Use of MI did not appear to lengthen the time of clinical visits, and in some cases may actually shorten them,” said Dr. Dempsey. In addition to analyzing whether MI and other components of the toolkit increased HPV vaccine uptake rates, Dr. Dempsey and her colleagues also plan to explore whether MI would be an effective approach to use when discussing immunizations with parents of infants and younger children.

The study was funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention, with survey administration supported by the National Institutes of Health. Dr. Dempsey reported no conflicts of interest.

[email protected]

On Twitter @karioakes

BALTIMORE – Motivational interviewing (MI) was well accepted by providers as part of a communication tool kit to improve human papillomavirus vaccine uptake, according to results of an eight-site study.

Overall, most of the 107 medical providers who participated in the cluster-randomized trial found MI to be a “somewhat useful” (47%) or “very useful” (31%) tactic to use when discussing human papillomavirus (HPV) vaccination with parents of adolescents. The overall amount of time that providers spent discussing vaccinations actually decreased after implementing MI; at the same time, providers felt that they had more power to influence parental decision-making when using MI techniques.

©Cathy Yeulet/Thinkstock

“Primary care providers given the Physician Communication Toolkit used MI frequently, and this use was generally sustained over time,” said lead author Amanda Dempsey, MD, who presented the findings during a poster symposium at the annual meeting of the Pediatric Academic Societies.

Motivational interviewing, an open-ended, nonjudgmental listening and communication style, was taught to providers in one 30-minute webinar and two 1-hour in-person role-playing sessions. Participants were able to practice using MI both in circumstances where parents were accepting of vaccination, and with vaccine-hesitant families.

Participating providers were surveyed pretraining and at 4, 7, and 10 months after the training to assess their practices in the preceding month. The two primary outcome measures assessed, and compared from baseline, were the estimated time spent discussing HPV vaccination with both vaccine-hesitant and nonhesitant families, and the providers’ perceived abilities to influence decisions about HPV. Dr. Dempsey and her colleagues also asked whether practitioners were actually using MI techniques with vaccine-hesitant parents, and whether they found the techniques useful in HPV vaccination discussions.

Dr. Dempsey, associate professor of pediatrics at Children’s Hospital Colorado in Aurora, said that uptake of MI was initially high and remained so. Three months after the intervention, 85% of providers reported they were using MI; at 9 months after the intervention, the figure was 72%.

Previous research has shown that providers generally do not communicate strong recommendations about HPV vaccination. “Providers often feel the parents will argue with them about it, and sometimes don’t even bring it up,” Dr. Dempsey said in an interview. “Anecdotally, providers found MI a useful way to frame the conversation, and they found it less confrontational.”

Overall, about three-quarters of providers responding to the sequential surveys were physicians, another 15%-20% were physician assistants, and the remainder were nurse practitioners. About one in four respondents were male. The pediatric and family medicine practices were approximately evenly divided between public and private clinics.

Although participation in the training and the subsequent surveys was voluntary, uptake was fairly high at participating clinics. The training was offered for 25 MOC (maintenance of certification) part 4 credits, which probably helped participation rates, said Dr. Dempsey.

The small sample size of the study, said Dr. Dempsey, limits the generalizability of the findings. However, the eight sites chosen represented a wide range of socioeconomic and cultural demographics in the patients served. Also, self-report of MI use may be subject to some bias. Finally, because this was a naturalistic study that allowed providers full discretion in using the various components of the Physician Communication Toolkit, it was not possible to perform a completely independent analysis of the effects of using MI apart from the other toolkit components.

“Use of MI did not appear to lengthen the time of clinical visits, and in some cases may actually shorten them,” said Dr. Dempsey. In addition to analyzing whether MI and other components of the toolkit increased HPV vaccine uptake rates, Dr. Dempsey and her colleagues also plan to explore whether MI would be an effective approach to use when discussing immunizations with parents of infants and younger children.

The study was funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention, with survey administration supported by the National Institutes of Health. Dr. Dempsey reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Gestational diabetes and prenatal progesterone use were among the maternal factors associated with increased risk of infantile hemangioma, a benign vascular neoplasm whose incidence has been steadily rising over the past several decades.

Data from a large longitudinal epidemiology study were used to explore the association of a number of maternal risk factors with infantile hemangiomas, said Jennifer Schoch, MD, who presented these findings in a poster session at the annual meeting of the Society for Pediatric Dermatology.

Kari Oakes/Frontline Medical News

After adjusting for gestational age and multiple gestations, the researchers found that infants born to mothers with gestational diabetes were more likely to have an infantile hemangioma (odds ratio, 1.79; P = .029). Maternal preeclampsia was even more strongly associated with infantile hemangioma (OR, 3.43, P = .017), as was prenatal progesterone use (OR, 2.25; P less than .001). Forceps-assisted vaginal delivery also increased the likelihood of infantile hemangioma (OR, 1.45; P = .035).

Low birth weight, prematurity, and being female and of non-Hispanic white race are some of the infant risk factors known to be associated with infantile hemangioma, but maternal risk factors in the development of infantile hemangioma are less clear, according to the researchers from the Mayo Clinic, Rochester, Minn. Some previous work has suggested that placental abnormalities and invasive procedures carried out during pregnancy, as well as the use of progesterone and corticosteroids during pregnancy, may increase the risk of infantile hemangiomas.

Using a retrospective case-control approach, the researchers used data from the 50-year-old Rochester Epidemiology Project. A chart review identified 869 mother-infant pairs with infantile hemangiomas and 869 age- and sex-matched control maternal-infant pairs whose infants did not have the condition. More than half (65%) of the infants in aggregate were girls (n = 561). Multivariable analysis was used to adjust for gestational age and multiple gestations.

Looking at the trends over time revealed that the rates of gestational diabetes, assisted reproduction techniques, and progesterone use during pregnancy have all increased during the same 35-year period of increased infantile hemangioma incidence, Dr. Schoch said in an interview.

Some earlier work suggests that infantile hemangiomas may arise from fetal placental progenitor cells. Since gestational diabetes can be associated with degradation of the placenta in late pregnancy, Dr. Schoch said that these effects on the placenta may have some connection to the increased risk of infantile hemangiomas in infants whose mothers have gestational diabetes.

Dr. Schoch, who is now professor of dermatology at the University of Florida, Gainesville, also noted that the study, completed during her fellowship at the Mayo Clinic, was limited by the low ethnic diversity of the study population, which draws from several counties in Minnesota and Wisconsin.

The Rochester Epidemiology Project is supported by the National Institutes of Health. The researchers reported having no financial disclosures.

MINNEAPOLIS – Gestational diabetes and prenatal progesterone use were among the maternal factors associated with increased risk of infantile hemangioma, a benign vascular neoplasm whose incidence has been steadily rising over the past several decades.

Data from a large longitudinal epidemiology study were used to explore the association of a number of maternal risk factors with infantile hemangiomas, said Jennifer Schoch, MD, who presented these findings in a poster session at the annual meeting of the Society for Pediatric Dermatology.

Kari Oakes/Frontline Medical News

After adjusting for gestational age and multiple gestations, the researchers found that infants born to mothers with gestational diabetes were more likely to have an infantile hemangioma (odds ratio, 1.79; P = .029). Maternal preeclampsia was even more strongly associated with infantile hemangioma (OR, 3.43, P = .017), as was prenatal progesterone use (OR, 2.25; P less than .001). Forceps-assisted vaginal delivery also increased the likelihood of infantile hemangioma (OR, 1.45; P = .035).

Low birth weight, prematurity, and being female and of non-Hispanic white race are some of the infant risk factors known to be associated with infantile hemangioma, but maternal risk factors in the development of infantile hemangioma are less clear, according to the researchers from the Mayo Clinic, Rochester, Minn. Some previous work has suggested that placental abnormalities and invasive procedures carried out during pregnancy, as well as the use of progesterone and corticosteroids during pregnancy, may increase the risk of infantile hemangiomas.

Using a retrospective case-control approach, the researchers used data from the 50-year-old Rochester Epidemiology Project. A chart review identified 869 mother-infant pairs with infantile hemangiomas and 869 age- and sex-matched control maternal-infant pairs whose infants did not have the condition. More than half (65%) of the infants in aggregate were girls (n = 561). Multivariable analysis was used to adjust for gestational age and multiple gestations.

Looking at the trends over time revealed that the rates of gestational diabetes, assisted reproduction techniques, and progesterone use during pregnancy have all increased during the same 35-year period of increased infantile hemangioma incidence, Dr. Schoch said in an interview.

Some earlier work suggests that infantile hemangiomas may arise from fetal placental progenitor cells. Since gestational diabetes can be associated with degradation of the placenta in late pregnancy, Dr. Schoch said that these effects on the placenta may have some connection to the increased risk of infantile hemangiomas in infants whose mothers have gestational diabetes.

Dr. Schoch, who is now professor of dermatology at the University of Florida, Gainesville, also noted that the study, completed during her fellowship at the Mayo Clinic, was limited by the low ethnic diversity of the study population, which draws from several counties in Minnesota and Wisconsin.

The Rochester Epidemiology Project is supported by the National Institutes of Health. The researchers reported having no financial disclosures.

MINNEAPOLIS – Gestational diabetes and prenatal progesterone use were among the maternal factors associated with increased risk of infantile hemangioma, a benign vascular neoplasm whose incidence has been steadily rising over the past several decades.

Data from a large longitudinal epidemiology study were used to explore the association of a number of maternal risk factors with infantile hemangiomas, said Jennifer Schoch, MD, who presented these findings in a poster session at the annual meeting of the Society for Pediatric Dermatology.

Kari Oakes/Frontline Medical News

After adjusting for gestational age and multiple gestations, the researchers found that infants born to mothers with gestational diabetes were more likely to have an infantile hemangioma (odds ratio, 1.79; P = .029). Maternal preeclampsia was even more strongly associated with infantile hemangioma (OR, 3.43, P = .017), as was prenatal progesterone use (OR, 2.25; P less than .001). Forceps-assisted vaginal delivery also increased the likelihood of infantile hemangioma (OR, 1.45; P = .035).

Low birth weight, prematurity, and being female and of non-Hispanic white race are some of the infant risk factors known to be associated with infantile hemangioma, but maternal risk factors in the development of infantile hemangioma are less clear, according to the researchers from the Mayo Clinic, Rochester, Minn. Some previous work has suggested that placental abnormalities and invasive procedures carried out during pregnancy, as well as the use of progesterone and corticosteroids during pregnancy, may increase the risk of infantile hemangiomas.

Using a retrospective case-control approach, the researchers used data from the 50-year-old Rochester Epidemiology Project. A chart review identified 869 mother-infant pairs with infantile hemangiomas and 869 age- and sex-matched control maternal-infant pairs whose infants did not have the condition. More than half (65%) of the infants in aggregate were girls (n = 561). Multivariable analysis was used to adjust for gestational age and multiple gestations.

Looking at the trends over time revealed that the rates of gestational diabetes, assisted reproduction techniques, and progesterone use during pregnancy have all increased during the same 35-year period of increased infantile hemangioma incidence, Dr. Schoch said in an interview.

Some earlier work suggests that infantile hemangiomas may arise from fetal placental progenitor cells. Since gestational diabetes can be associated with degradation of the placenta in late pregnancy, Dr. Schoch said that these effects on the placenta may have some connection to the increased risk of infantile hemangiomas in infants whose mothers have gestational diabetes.

Dr. Schoch, who is now professor of dermatology at the University of Florida, Gainesville, also noted that the study, completed during her fellowship at the Mayo Clinic, was limited by the low ethnic diversity of the study population, which draws from several counties in Minnesota and Wisconsin.

The Rochester Epidemiology Project is supported by the National Institutes of Health. The researchers reported having no financial disclosures.

MINNEAPOLIS – Gestational diabetes and prenatal progesterone use were among the maternal factors associated with increased risk of infantile hemangioma, a benign vascular neoplasm whose incidence has been steadily rising over the past several decades.

Data from a large longitudinal epidemiology study were used to explore the association of a number of maternal risk factors with infantile hemangiomas, said Jennifer Schoch, MD, who presented these findings in a poster session at the annual meeting of the Society for Pediatric Dermatology.

Kari Oakes/Frontline Medical News

After adjusting for gestational age and multiple gestations, the researchers found that infants born to mothers with gestational diabetes were more likely to have an infantile hemangioma (odds ratio, 1.79; P = .029). Maternal preeclampsia was even more strongly associated with infantile hemangioma (OR, 3.43, P = .017), as was prenatal progesterone use (OR, 2.25; P less than .001). Forceps-assisted vaginal delivery also increased the likelihood of infantile hemangioma (OR, 1.45; P = .035).

Low birth weight, prematurity, and being female and of non-Hispanic white race are some of the infant risk factors known to be associated with infantile hemangioma, but maternal risk factors in the development of infantile hemangioma are less clear, according to the researchers from the Mayo Clinic, Rochester, Minn. Some previous work has suggested that placental abnormalities and invasive procedures carried out during pregnancy, as well as the use of progesterone and corticosteroids during pregnancy, may increase the risk of infantile hemangiomas.

Using a retrospective case-control approach, the researchers used data from the 50-year-old Rochester Epidemiology Project. A chart review identified 869 mother-infant pairs with infantile hemangiomas and 869 age- and sex-matched control maternal-infant pairs whose infants did not have the condition. More than half (65%) of the infants in aggregate were girls (n = 561). Multivariable analysis was used to adjust for gestational age and multiple gestations.

Looking at the trends over time revealed that the rates of gestational diabetes, assisted reproduction techniques, and progesterone use during pregnancy have all increased during the same 35-year period of increased infantile hemangioma incidence, Dr. Schoch said in an interview.

Some earlier work suggests that infantile hemangiomas may arise from fetal placental progenitor cells. Since gestational diabetes can be associated with degradation of the placenta in late pregnancy, Dr. Schoch said that these effects on the placenta may have some connection to the increased risk of infantile hemangiomas in infants whose mothers have gestational diabetes.

Dr. Schoch, who is now professor of dermatology at the University of Florida, Gainesville, also noted that the study, completed during her fellowship at the Mayo Clinic, was limited by the low ethnic diversity of the study population, which draws from several counties in Minnesota and Wisconsin.

The Rochester Epidemiology Project is supported by the National Institutes of Health. The researchers reported having no financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Gestational diabetes and prenatal progesterone use were among the maternal factors associated with increased risk of infantile hemangioma, a benign vascular neoplasm whose incidence has been steadily rising over the past several decades.

Data from a large longitudinal epidemiology study were used to explore the association of a number of maternal risk factors with infantile hemangiomas, said Jennifer Schoch, MD, who presented these findings in a poster session at the annual meeting of the Society for Pediatric Dermatology.

Kari Oakes/Frontline Medical News

After adjusting for gestational age and multiple gestations, the researchers found that infants born to mothers with gestational diabetes were more likely to have an infantile hemangioma (odds ratio, 1.79; P = .029). Maternal preeclampsia was even more strongly associated with infantile hemangioma (OR, 3.43, P = .017), as was prenatal progesterone use (OR, 2.25; P less than .001). Forceps-assisted vaginal delivery also increased the likelihood of infantile hemangioma (OR, 1.45; P = .035).

Low birth weight, prematurity, and being female and of non-Hispanic white race are some of the infant risk factors known to be associated with infantile hemangioma, but maternal risk factors in the development of infantile hemangioma are less clear, according to the researchers from the Mayo Clinic, Rochester, Minn. Some previous work has suggested that placental abnormalities and invasive procedures carried out during pregnancy, as well as the use of progesterone and corticosteroids during pregnancy, may increase the risk of infantile hemangiomas.

Using a retrospective case-control approach, the researchers used data from the 50-year-old Rochester Epidemiology Project. A chart review identified 869 mother-infant pairs with infantile hemangiomas and 869 age- and sex-matched control maternal-infant pairs whose infants did not have the condition. More than half (65%) of the infants in aggregate were girls (n = 561). Multivariable analysis was used to adjust for gestational age and multiple gestations.

Looking at the trends over time revealed that the rates of gestational diabetes, assisted reproduction techniques, and progesterone use during pregnancy have all increased during the same 35-year period of increased infantile hemangioma incidence, Dr. Schoch said in an interview.

Some earlier work suggests that infantile hemangiomas may arise from fetal placental progenitor cells. Since gestational diabetes can be associated with degradation of the placenta in late pregnancy, Dr. Schoch said that these effects on the placenta may have some connection to the increased risk of infantile hemangiomas in infants whose mothers have gestational diabetes.

Dr. Schoch, who is now professor of dermatology at the University of Florida, Gainesville, also noted that the study, completed during her fellowship at the Mayo Clinic, was limited by the low ethnic diversity of the study population, which draws from several counties in Minnesota and Wisconsin.

The Rochester Epidemiology Project is supported by the National Institutes of Health. The researchers reported having no financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Gestational diabetes and prenatal progesterone use were among the maternal factors associated with increased risk of infantile hemangioma, a benign vascular neoplasm whose incidence has been steadily rising over the past several decades.

Data from a large longitudinal epidemiology study were used to explore the association of a number of maternal risk factors with infantile hemangiomas, said Jennifer Schoch, MD, who presented these findings in a poster session at the annual meeting of the Society for Pediatric Dermatology.

Kari Oakes/Frontline Medical News

After adjusting for gestational age and multiple gestations, the researchers found that infants born to mothers with gestational diabetes were more likely to have an infantile hemangioma (odds ratio, 1.79; P = .029). Maternal preeclampsia was even more strongly associated with infantile hemangioma (OR, 3.43, P = .017), as was prenatal progesterone use (OR, 2.25; P less than .001). Forceps-assisted vaginal delivery also increased the likelihood of infantile hemangioma (OR, 1.45; P = .035).

Low birth weight, prematurity, and being female and of non-Hispanic white race are some of the infant risk factors known to be associated with infantile hemangioma, but maternal risk factors in the development of infantile hemangioma are less clear, according to the researchers from the Mayo Clinic, Rochester, Minn. Some previous work has suggested that placental abnormalities and invasive procedures carried out during pregnancy, as well as the use of progesterone and corticosteroids during pregnancy, may increase the risk of infantile hemangiomas.

Using a retrospective case-control approach, the researchers used data from the 50-year-old Rochester Epidemiology Project. A chart review identified 869 mother-infant pairs with infantile hemangiomas and 869 age- and sex-matched control maternal-infant pairs whose infants did not have the condition. More than half (65%) of the infants in aggregate were girls (n = 561). Multivariable analysis was used to adjust for gestational age and multiple gestations.

Looking at the trends over time revealed that the rates of gestational diabetes, assisted reproduction techniques, and progesterone use during pregnancy have all increased during the same 35-year period of increased infantile hemangioma incidence, Dr. Schoch said in an interview.

Some earlier work suggests that infantile hemangiomas may arise from fetal placental progenitor cells. Since gestational diabetes can be associated with degradation of the placenta in late pregnancy, Dr. Schoch said that these effects on the placenta may have some connection to the increased risk of infantile hemangiomas in infants whose mothers have gestational diabetes.

Dr. Schoch, who is now professor of dermatology at the University of Florida, Gainesville, also noted that the study, completed during her fellowship at the Mayo Clinic, was limited by the low ethnic diversity of the study population, which draws from several counties in Minnesota and Wisconsin.

The Rochester Epidemiology Project is supported by the National Institutes of Health. The researchers reported having no financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS, MINN. – Indoor tanning is a significant contributor to the U.S. skin cancer epidemic and represents a 100% preventable source of exposure to these cancers. Understanding exactly who is using indoor tanning – and why – can provide insight and leverage to help change behavior, according to Cindy Firkins Smith, MD, adjunct professor of dermatology at the University of Minnesota, Minneapolis.

Dr. Smith noted that the typical indoor tanning bed user is female and between 17 and 30 years old. Other aspects of her lifestyle may be unhealthy; for example, she may smoke cigarettes, have an unhealthy pattern of alcohol consumption, and make unhealthy food choices (Cancer Causes Control 2006 June. doi:10.1007/s10552-005-0453-9). She also is likely to watch beauty-focused reality TV shows (J Am Acad Dermatol 2013 May. doi:10.1016/j.jaad.2012.09.055) and is likely to objectify her own body, seeing it as something to be viewed and judged (Arch Dermatol 2009 Sep 1. doi:10.1001/archdermatol.2009.190).

©Vidmantas Goldbergas/Thinkstock

Tanning is a behavior that provides relaxation and positive emotions, and she receives support for this behavior from family and friends. “Tanning often starts with mom, which is one reason that parental permission legislation doesn’t work,” she said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Smith said that up to 30 million people tan indoors every year. Rates of tanning for teenage girls are very high: up to 40% of American teenagers use indoor tanning, and 20%-30% of all 18- to 29-year-olds have used a tanning bed in the previous year (Jama Dermatol 2014 April doi: 10.1001/jamadermatol.2013.6896).

The ubiquity of tanning salons contributes to the problem, said Dr. Smith. “More is not better; in the largest U.S. cities, tanning salons outnumber [both] Starbucks and McDonald’s,” she said, noting that studies have shown that both proximity to tanning salons and the low cost of tanning encourage their use (Am J Prev Med. 2009 Mar 36[3]:243-6).

A 2015 study surveyed 125 colleges, finding that 48% had indoor tanning facilities in their campus or off-campus housing. College cash cards were acceptable payment at 14.4% of colleges, and 96% of off-campus housing facilities that offered tanning provided it as a free “perk” to residents (JAMA Dermatol 2015 Jan. doi: 10.1001/jamadermatol.2014.3590).

Further, some data suggest that tanning really can be addictive for some patients. Ultraviolet light exposure has been shown to “light up” pleasure centers in PET-CT studies, and some frequent tanners report relaxation and pleasure from tanning as well as craving and feelings of withdrawal when they miss sessions. Dr. Smith said she does not hesitate to refer teen patients to mental health providers if there are concerns about mood and depression.

Having an understanding of patient motivations to tan can help in getting patients to take steps toward change, said Dr. Smith. “What can we do? We can actually do a lot. We have a lot more influence than we think we do.”

At the level of the individual patient, just opening up a conversation can make a big difference. “We assume we know why teenagers go to a tanning booth. But do we? When you notice a young woman who’s been to a tanning booth, ask why,” using a nonjudgmental approach to begin a dialogue about the near-term and long-term dangers of tanning. A positive approach is key, noted Dr. Smith. “Focusing on the benefits of avoiding UV tanning is more effective than a heavy reliance on scare tactics,” she said. Also, “multiple interventions work better.”

Before-and-after photos of celebrities whose appearance has been affected by photoaging can be effective. Another tactic with a more positive spin is to share images of celebrities who have chosen not to tan and who celebrate their fair skin. These conversations are particularly important at prom time, peak tanning season for many young women, said Dr. Smith. She has a portfolio of photos showing fair-skinned women wearing high-contrast gowns, which she says are more flattering for pale skin than white or nude colors.

For patients who still want that tan look, “Tanning for reasons of appearance can be satisfied with sunless tanners,” said Dr. Smith. The most common ingredient in sunless tanners is dihydroxyacetone (DHA), which was approved in the 1970s for topical use. However, the Food and Drug Administration issued a warning in 2011 about spray tanning, noting that the “industry has not provided safety data to FDA in order for the agency to consider approving it for … ‘misting’ from tanning booths.” The FDA’s specific concern had to do with the unknown safety of ingestion, inhalation, and mucous membrane exposure that can result from spray tanning.

Moving to the legislative and policy level, change can be achieved when stakeholders band together to “ban the tan,” said Dr. Smith. “The best way to do it is with a village. It really takes a lot of people to do this.”

There are solid epidemiologic and economic reasons to focus on the skin cancer epidemic, said Dr. Smith. Skin cancer is now the most common cancer in the United States, and more new cases “are diagnosed each year than breast, prostate, lung, and colon cancers combined,” she said. Of nonmelanoma skin cancers, 90% are thought to be UV-related, and “the vast majority of mutations found in melanoma are caused by UV radiation.”

Skin cancers cost the United States over $8 billion annually, and although promising new immunotherapies are extending the lives of those with melanoma, these treatments cost hundreds of thousands of dollars a year. “This type of treatment is unaffordable for our system,” said Dr. Smith.

Progress is being made, she said, despite industry opposition. Individual states have regulated or banned tanning for minors, and at the federal level, tanning beds are now considered by the FDA to be Class II (moderate-risk) medical devices, a step up from their previous classification as the lowest-risk Class I devices, “The same as a tongue blade,” she said.

Dr. Smith had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS, MINN. – Indoor tanning is a significant contributor to the U.S. skin cancer epidemic and represents a 100% preventable source of exposure to these cancers. Understanding exactly who is using indoor tanning – and why – can provide insight and leverage to help change behavior, according to Cindy Firkins Smith, MD, adjunct professor of dermatology at the University of Minnesota, Minneapolis.

Dr. Smith noted that the typical indoor tanning bed user is female and between 17 and 30 years old. Other aspects of her lifestyle may be unhealthy; for example, she may smoke cigarettes, have an unhealthy pattern of alcohol consumption, and make unhealthy food choices (Cancer Causes Control 2006 June. doi:10.1007/s10552-005-0453-9). She also is likely to watch beauty-focused reality TV shows (J Am Acad Dermatol 2013 May. doi:10.1016/j.jaad.2012.09.055) and is likely to objectify her own body, seeing it as something to be viewed and judged (Arch Dermatol 2009 Sep 1. doi:10.1001/archdermatol.2009.190).

©Vidmantas Goldbergas/Thinkstock

Tanning is a behavior that provides relaxation and positive emotions, and she receives support for this behavior from family and friends. “Tanning often starts with mom, which is one reason that parental permission legislation doesn’t work,” she said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Smith said that up to 30 million people tan indoors every year. Rates of tanning for teenage girls are very high: up to 40% of American teenagers use indoor tanning, and 20%-30% of all 18- to 29-year-olds have used a tanning bed in the previous year (Jama Dermatol 2014 April doi: 10.1001/jamadermatol.2013.6896).

The ubiquity of tanning salons contributes to the problem, said Dr. Smith. “More is not better; in the largest U.S. cities, tanning salons outnumber [both] Starbucks and McDonald’s,” she said, noting that studies have shown that both proximity to tanning salons and the low cost of tanning encourage their use (Am J Prev Med. 2009 Mar 36[3]:243-6).

A 2015 study surveyed 125 colleges, finding that 48% had indoor tanning facilities in their campus or off-campus housing. College cash cards were acceptable payment at 14.4% of colleges, and 96% of off-campus housing facilities that offered tanning provided it as a free “perk” to residents (JAMA Dermatol 2015 Jan. doi: 10.1001/jamadermatol.2014.3590).

Further, some data suggest that tanning really can be addictive for some patients. Ultraviolet light exposure has been shown to “light up” pleasure centers in PET-CT studies, and some frequent tanners report relaxation and pleasure from tanning as well as craving and feelings of withdrawal when they miss sessions. Dr. Smith said she does not hesitate to refer teen patients to mental health providers if there are concerns about mood and depression.

Having an understanding of patient motivations to tan can help in getting patients to take steps toward change, said Dr. Smith. “What can we do? We can actually do a lot. We have a lot more influence than we think we do.”

At the level of the individual patient, just opening up a conversation can make a big difference. “We assume we know why teenagers go to a tanning booth. But do we? When you notice a young woman who’s been to a tanning booth, ask why,” using a nonjudgmental approach to begin a dialogue about the near-term and long-term dangers of tanning. A positive approach is key, noted Dr. Smith. “Focusing on the benefits of avoiding UV tanning is more effective than a heavy reliance on scare tactics,” she said. Also, “multiple interventions work better.”

Before-and-after photos of celebrities whose appearance has been affected by photoaging can be effective. Another tactic with a more positive spin is to share images of celebrities who have chosen not to tan and who celebrate their fair skin. These conversations are particularly important at prom time, peak tanning season for many young women, said Dr. Smith. She has a portfolio of photos showing fair-skinned women wearing high-contrast gowns, which she says are more flattering for pale skin than white or nude colors.

For patients who still want that tan look, “Tanning for reasons of appearance can be satisfied with sunless tanners,” said Dr. Smith. The most common ingredient in sunless tanners is dihydroxyacetone (DHA), which was approved in the 1970s for topical use. However, the Food and Drug Administration issued a warning in 2011 about spray tanning, noting that the “industry has not provided safety data to FDA in order for the agency to consider approving it for … ‘misting’ from tanning booths.” The FDA’s specific concern had to do with the unknown safety of ingestion, inhalation, and mucous membrane exposure that can result from spray tanning.

Moving to the legislative and policy level, change can be achieved when stakeholders band together to “ban the tan,” said Dr. Smith. “The best way to do it is with a village. It really takes a lot of people to do this.”

There are solid epidemiologic and economic reasons to focus on the skin cancer epidemic, said Dr. Smith. Skin cancer is now the most common cancer in the United States, and more new cases “are diagnosed each year than breast, prostate, lung, and colon cancers combined,” she said. Of nonmelanoma skin cancers, 90% are thought to be UV-related, and “the vast majority of mutations found in melanoma are caused by UV radiation.”

Skin cancers cost the United States over $8 billion annually, and although promising new immunotherapies are extending the lives of those with melanoma, these treatments cost hundreds of thousands of dollars a year. “This type of treatment is unaffordable for our system,” said Dr. Smith.

Progress is being made, she said, despite industry opposition. Individual states have regulated or banned tanning for minors, and at the federal level, tanning beds are now considered by the FDA to be Class II (moderate-risk) medical devices, a step up from their previous classification as the lowest-risk Class I devices, “The same as a tongue blade,” she said.

Dr. Smith had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS, MINN. – Indoor tanning is a significant contributor to the U.S. skin cancer epidemic and represents a 100% preventable source of exposure to these cancers. Understanding exactly who is using indoor tanning – and why – can provide insight and leverage to help change behavior, according to Cindy Firkins Smith, MD, adjunct professor of dermatology at the University of Minnesota, Minneapolis.

Dr. Smith noted that the typical indoor tanning bed user is female and between 17 and 30 years old. Other aspects of her lifestyle may be unhealthy; for example, she may smoke cigarettes, have an unhealthy pattern of alcohol consumption, and make unhealthy food choices (Cancer Causes Control 2006 June. doi:10.1007/s10552-005-0453-9). She also is likely to watch beauty-focused reality TV shows (J Am Acad Dermatol 2013 May. doi:10.1016/j.jaad.2012.09.055) and is likely to objectify her own body, seeing it as something to be viewed and judged (Arch Dermatol 2009 Sep 1. doi:10.1001/archdermatol.2009.190).

©Vidmantas Goldbergas/Thinkstock

Tanning is a behavior that provides relaxation and positive emotions, and she receives support for this behavior from family and friends. “Tanning often starts with mom, which is one reason that parental permission legislation doesn’t work,” she said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Smith said that up to 30 million people tan indoors every year. Rates of tanning for teenage girls are very high: up to 40% of American teenagers use indoor tanning, and 20%-30% of all 18- to 29-year-olds have used a tanning bed in the previous year (Jama Dermatol 2014 April doi: 10.1001/jamadermatol.2013.6896).

The ubiquity of tanning salons contributes to the problem, said Dr. Smith. “More is not better; in the largest U.S. cities, tanning salons outnumber [both] Starbucks and McDonald’s,” she said, noting that studies have shown that both proximity to tanning salons and the low cost of tanning encourage their use (Am J Prev Med. 2009 Mar 36[3]:243-6).

A 2015 study surveyed 125 colleges, finding that 48% had indoor tanning facilities in their campus or off-campus housing. College cash cards were acceptable payment at 14.4% of colleges, and 96% of off-campus housing facilities that offered tanning provided it as a free “perk” to residents (JAMA Dermatol 2015 Jan. doi: 10.1001/jamadermatol.2014.3590).

Further, some data suggest that tanning really can be addictive for some patients. Ultraviolet light exposure has been shown to “light up” pleasure centers in PET-CT studies, and some frequent tanners report relaxation and pleasure from tanning as well as craving and feelings of withdrawal when they miss sessions. Dr. Smith said she does not hesitate to refer teen patients to mental health providers if there are concerns about mood and depression.

Having an understanding of patient motivations to tan can help in getting patients to take steps toward change, said Dr. Smith. “What can we do? We can actually do a lot. We have a lot more influence than we think we do.”

At the level of the individual patient, just opening up a conversation can make a big difference. “We assume we know why teenagers go to a tanning booth. But do we? When you notice a young woman who’s been to a tanning booth, ask why,” using a nonjudgmental approach to begin a dialogue about the near-term and long-term dangers of tanning. A positive approach is key, noted Dr. Smith. “Focusing on the benefits of avoiding UV tanning is more effective than a heavy reliance on scare tactics,” she said. Also, “multiple interventions work better.”

Before-and-after photos of celebrities whose appearance has been affected by photoaging can be effective. Another tactic with a more positive spin is to share images of celebrities who have chosen not to tan and who celebrate their fair skin. These conversations are particularly important at prom time, peak tanning season for many young women, said Dr. Smith. She has a portfolio of photos showing fair-skinned women wearing high-contrast gowns, which she says are more flattering for pale skin than white or nude colors.

For patients who still want that tan look, “Tanning for reasons of appearance can be satisfied with sunless tanners,” said Dr. Smith. The most common ingredient in sunless tanners is dihydroxyacetone (DHA), which was approved in the 1970s for topical use. However, the Food and Drug Administration issued a warning in 2011 about spray tanning, noting that the “industry has not provided safety data to FDA in order for the agency to consider approving it for … ‘misting’ from tanning booths.” The FDA’s specific concern had to do with the unknown safety of ingestion, inhalation, and mucous membrane exposure that can result from spray tanning.

Moving to the legislative and policy level, change can be achieved when stakeholders band together to “ban the tan,” said Dr. Smith. “The best way to do it is with a village. It really takes a lot of people to do this.”

There are solid epidemiologic and economic reasons to focus on the skin cancer epidemic, said Dr. Smith. Skin cancer is now the most common cancer in the United States, and more new cases “are diagnosed each year than breast, prostate, lung, and colon cancers combined,” she said. Of nonmelanoma skin cancers, 90% are thought to be UV-related, and “the vast majority of mutations found in melanoma are caused by UV radiation.”

Skin cancers cost the United States over $8 billion annually, and although promising new immunotherapies are extending the lives of those with melanoma, these treatments cost hundreds of thousands of dollars a year. “This type of treatment is unaffordable for our system,” said Dr. Smith.

Progress is being made, she said, despite industry opposition. Individual states have regulated or banned tanning for minors, and at the federal level, tanning beds are now considered by the FDA to be Class II (moderate-risk) medical devices, a step up from their previous classification as the lowest-risk Class I devices, “The same as a tongue blade,” she said.

Dr. Smith had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

*A previous version of this article misstated the number of patients who experienced SIB events.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

*A previous version of this article misstated the number of patients who experienced SIB events.

A Food and Drug Administration advisory committee has unanimously supported approval of the monoclonal antibody brodalumab for the treatment of moderate to severe plaque psoriasis, with the majority recommending risk management options beyond labeling to address concerns about the six completed suicides among patients treated with brodalumab in clinical trials.

Though no members of the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee disputed the drug’s efficacy for plaque psoriasis, the possibility of a signal for suicidal ideation and behavior (SIB) among the brodalumab group prompted the committee’s chair, Michael Bigby, M.D., to remark, “The big problem is that you have six completed suicides. … I would say it’s a fairly big number for a randomized controlled trial. Patients and clinicians need to be aware of this as a fact.”

Dr. Bigby, professor of dermatology at Harvard Medical School, Boston, headed the 18-member panel, which included dermatologists, psychiatrists, and cardiologists. Fourteen members voted in favor of approval with risk management measures beyond labeling; four members voted for approval with labeling alone.

Brodalumab targets interleukin-17 receptors, inhibiting IL-17 uptake and thus blocking the pathway responsible for the cutaneous and systemic signs and symptoms of psoriasis. The pivotal phase III brodalumab studies, AMAGINE-1, -2, and -3, enrolled a total of 4,373 patients with moderate to severe plaque psoriasis. AMAGINE-1 enrolled 661 patients in a 1:1:1 ratio to a randomized, double-blind placebo-controlled study that included two doses of brodalumab: 210 mg and 140 mg. The placebo-controlled phase of the study ran for 12 weeks, followed by a withdrawal and retreatment phase, and after 52 weeks, by an open label long-term extension phase.

AMAGINE-2 (1,831 patients) and AMAGINE-3 (1,881 patients) were identically designed studies that pitted both doses of brodalumab against an active comparator, ustekinumab (Stelara), as well as placebo, in a 2:2:1:1 ratio. This double-blind phase of the study also lasted 12 weeks. During weeks 12-52, patients on the brodalumab arms continued, with an exploration of wider-dose intervals for the 140-mg dose. Patients also continued with ustekinumab, with a rescue option to transition to brodalumab 210 mg. The placebo group could continue on brodalumab 210 mg as well. These two studies also had an open label long-term extension phase.

At the 12-week mark in AMAGINE-1, 41.9% of patients achieved the coprimary endpoint of 100% reduction in the Psoriasis Area and Severity Index (PASI 100) score, compared with 0.5% of those on placebo (P less than .001). AMAGINE-2 and -3 saw 44.4% and 36.7% of the brodalumab 210-mg arms achieving PASI 100 at the 12-week mark, respectively. These figures were significantly higher than the 21.7% and 18.5% reaching PASI 100 on ustekinumab (P less than .001), as well as significantly higher than the less than 1% of patients in the placebo arm who reached that endpoint.

At the end of 52 weeks, 51% of those on brodalumab 210 mg had completely clear skin, compared with 28.1% of the patients receiving ustekinumab (P less than .001).

The safety analysis for brodalumab showed that the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and arthralgia; of these, the last two were considered adverse drug reactions. At 52 weeks, those on brodalumab had a slightly greater risk of having nonserious fungal infections than did those on ustekinumab. Overall, however, there was no difference between the brodalumab and ustekinumab arms at week 52 for treatment-emergent adverse events or for serious adverse events.

A cluster of SIB events occurred in 2013 and 2014 during the clinical trials, and the sponsor consulted the FDA. Additional monitoring for suicidal ideation and depression via the Columbia Suicide Severity Rating Scale (C-SSRS) and the Patient Health Questionnaire (PHQ) were implemented at a point where 84% of trial patients were already in the uncontrolled open label extension stage of the trial; in addition, a retrospective data review searched for suicidal ideation and attempts before the implementation of these two tools.

A total of six brodalumab patients completed suicide in all clinical trials, including those for psoriatic arthritis and RA. Suicides included two during the 12- to 52-week follow-up and four during the long-term follow-up phase. Another 29 patients attempted suicide, had intentional self-injury, or had suicidal ideation during these phases of the study, for a total of 35 SIB events. (SIB includes completed suicide, suicide attempt, suicide behavior, and suicide ideation.)*

The significance of the number of completed suicides was difficult to ascertain, given the increased baseline prevalence of depression and related illnesses among patients with psoriasis. Compared with the general population, individuals with psoriasis have hazard ratios of 1.39, 1.31, and 1.44 for depression, anxiety, and suicidality, according to a cohort study cited by Robert Levin, M.D. , director of the division of pharmacovigilance I at the FDA’s Center for Drug Evaluation and Research (CDER).

In addition, monitoring for suicidal ideation and attempts was stepped up during the course of the clinical trials. Brodalumab’s sponsor, Valeant Pharmaceuticals, noted that the rates of suicidal ideation and attempts increased after implementation of the C-SSRS, while other neuropsychiatric symptoms remained stable or declined during the course of the studies. “This makes us think this is ascertainment bias,” said Valeant consultant Lauren Marangell, M.D., a psychiatrist and president of Brain Health Consultants.

Dr. Marangell also reported that, after stratification for preexisting psychiatric comorbidities and risk factors, “there is no question that the rate of SIB is higher in both arms with patients with baseline risk factors.” The FDA’s data analysis showed an 18-fold increase in the rate of SIB for brodalumab arm participants with a prior history of suicidality.

During its presentation, Valeant also pointed out that patients with histories of drug and alcohol abuse, depression, and suicidality were not specifically excluded from the clinical trials. This differentiates the brodalumab program from other biologic studies, “making the studies more characteristic of the real world,” said R.K. Pillai, Ph.D., Valeant vice president.

Dr. Levin’s analysis, one of several independent analyses conducted by different FDA divisions, found that the data were inconclusive. “We currently can’t conclude whether or not these are drug-related risks,” he said. Considering the critical severity of suicide as an outcome, “we must consider the application and regulatory actions carefully.”

Jean Kim, M.D., medical officer in CDER’s division of psychiatry products (DPP), noted that the number of suicides seen in the brodalumab trials “is higher than typically seen in DPP’s large psychiatric drug trials, which involve populations with higher psychiatric morbidity than patients with psoriasis.”

Patients with psoriasis are also known to have a baseline elevated risk of cardiovascular disease, and no committee member felt the brodalumab data showed any additional signal for major adverse cardiovascular events (MACEs) beyond what would be suspected in this population. “I don’t right now see a safety signal for MACE,” said panelist Michael Blaha, M.D., a cardiologist and director of clinical research at Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore. He noted, however, that research is ongoing to elucidate the relationship between cytokine levels and MACE. “This question about whether cytokines raise or reduce rates for [cardiovascular] events is an open one.”

One of the dermatologists on the committee, Lynn Drake, M.D., said that her decision making was influenced by the disease burden psoriasis inflicts on the patients she sees in her daily practice. “These patients are ill. People tend to think it’s just skin disease. It is not just skin disease. … I’d hate to see our patients deprived of a drug that might help alleviate their symptoms,” said Dr. Drake.

Though committee members voiced some disagreement about whether a patient registry should be established, and if it should be voluntary, they were in agreement that patients and prescribers both be aware of the potential risks of brodalumab, without making any risk management strategy so burdensome that appropriate patients would be deterred from considering the medication. Psoriasis, Dr. Drake said, “is a devastating disease. We need this in our armamentarium.”

The proposed dosing for brodalumab is 210 mg injected subcutaneously weekly for 3 weeks, followed by 210 mg every 2 weeks thereafter.

The FDA usually follows the recommendations of its advisory committees. The panelists had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

*A previous version of this article misstated the number of patients who experienced SIB events.

BOSTON – Almost half of all sand and water samples taken from Midwestern freshwater public beaches tested positive for Staphylococcus aureus isolates during the summertime, but numbers fell dramatically in the fall and spring.

Overall, according to a study of 10 public beaches in Ohio, almost half of the isolates were resistant to erythromycin, 41% were multidrug resistant, and about 7% were methicillin-resistant S. aureus (MRSA).

In addition, among the 70 S. aureus isolates, 21.4% had the Panton-Valentine leukocidin (PVL) gene, which encodes for a pore-forming toxin identified as a virulence factor in some strains of staphylococcus. The study results were presented by Dipendra Thapaliya, a research associate at Kent State University, Ohio,, during a poster session at the annual meeting of the American Society for Microbiology.

Courtesy Tara Smith

In light of these findings, the study’s senior author, Tara Smith, PhD, professor of epidemiology at the university, said in an interview that beachgoers should take reasonable precautions, including washing lake water and sand off young children upon returning home, and making sure to shower at the beach if facilities are available.

“Staphylococcus does well in a salty environment, but it is a fairly hardy organism,” Dr. Smith said, noting that S. aureus has been found in the sand and water of marine beaches, but it has been less well studied in freshwater environments.

Public beaches in Ohio were the source of the samples. Some sampling was done along the shores of Lake Erie, but smaller inland lakes also were tested, In all, 280 sand and water samples were collected in a 3:1 water to sand ratio.

The samples were incubated and plated for culture and subculture according to established methods, and then tested for S. aureus via catalase and coagulase testing, as well as latex agglutination testing. Isolates were then subjected to antimicrobial susceptibility testing, as well as polymerase chain reaction (PCR) testing for the PVL gene and for the mecA genes found in MRSA. Final isolate identification was achieved by staphylococcal protein A (spa) and multilocus sequence typing.

Of the 27 spa types found from 70 isolates, two common strains, t008 and t002, were the most frequently detected. One livestock-associated strain, t571, was also identified.

Though beaches are frequently contaminated with E. coli and other enteric pathogens, the source is often birds or other wildlife, said Dr. Smith. To try to ascertain the source of the staphylococcus in the summer samples, Mr. Thapaliya and his collaborators repeated testing during the winter months and in the spring, before beachgoers had spent time at the waterside.

Those samples from the months when the beaches were empty of people showed much lower levels of S. aureus: In the summer, S. aureus isolates were found in almost half of the samples obtained (55/120, 45.8%). By contrast, only 5 of the 120 fall samples (4.8%) and 4 of the 40 spring samples (10%) were positive for S. aureus.

“The high prevalence of S. aureus in summer months and presence of human-associated strains may indicate the possible role of human presence in S. aureus contamination in beach water and sand. However, we need further study to confirm such a conclusion,” wrote Mr. Thapaliya and his coauthors.

To that end, Dr. Smith said that another, stronger piece of supporting evidence that the S. aureus does come from “the crush of human bathers” would be to identify and match isolates from individuals who frequent the beaches with isolates found in sand and water. Dr. Smith said that she and her team are currently seeking funding to carry out these next steps.

The investigators reported no relevant disclosures.

[email protected]

On Twitter @karioakes

BOSTON – Almost half of all sand and water samples taken from Midwestern freshwater public beaches tested positive for Staphylococcus aureus isolates during the summertime, but numbers fell dramatically in the fall and spring.

Overall, according to a study of 10 public beaches in Ohio, almost half of the isolates were resistant to erythromycin, 41% were multidrug resistant, and about 7% were methicillin-resistant S. aureus (MRSA).

In addition, among the 70 S. aureus isolates, 21.4% had the Panton-Valentine leukocidin (PVL) gene, which encodes for a pore-forming toxin identified as a virulence factor in some strains of staphylococcus. The study results were presented by Dipendra Thapaliya, a research associate at Kent State University, Ohio,, during a poster session at the annual meeting of the American Society for Microbiology.

Courtesy Tara Smith

In light of these findings, the study’s senior author, Tara Smith, PhD, professor of epidemiology at the university, said in an interview that beachgoers should take reasonable precautions, including washing lake water and sand off young children upon returning home, and making sure to shower at the beach if facilities are available.

“Staphylococcus does well in a salty environment, but it is a fairly hardy organism,” Dr. Smith said, noting that S. aureus has been found in the sand and water of marine beaches, but it has been less well studied in freshwater environments.

Public beaches in Ohio were the source of the samples. Some sampling was done along the shores of Lake Erie, but smaller inland lakes also were tested, In all, 280 sand and water samples were collected in a 3:1 water to sand ratio.

The samples were incubated and plated for culture and subculture according to established methods, and then tested for S. aureus via catalase and coagulase testing, as well as latex agglutination testing. Isolates were then subjected to antimicrobial susceptibility testing, as well as polymerase chain reaction (PCR) testing for the PVL gene and for the mecA genes found in MRSA. Final isolate identification was achieved by staphylococcal protein A (spa) and multilocus sequence typing.

Of the 27 spa types found from 70 isolates, two common strains, t008 and t002, were the most frequently detected. One livestock-associated strain, t571, was also identified.

Though beaches are frequently contaminated with E. coli and other enteric pathogens, the source is often birds or other wildlife, said Dr. Smith. To try to ascertain the source of the staphylococcus in the summer samples, Mr. Thapaliya and his collaborators repeated testing during the winter months and in the spring, before beachgoers had spent time at the waterside.

Those samples from the months when the beaches were empty of people showed much lower levels of S. aureus: In the summer, S. aureus isolates were found in almost half of the samples obtained (55/120, 45.8%). By contrast, only 5 of the 120 fall samples (4.8%) and 4 of the 40 spring samples (10%) were positive for S. aureus.

“The high prevalence of S. aureus in summer months and presence of human-associated strains may indicate the possible role of human presence in S. aureus contamination in beach water and sand. However, we need further study to confirm such a conclusion,” wrote Mr. Thapaliya and his coauthors.

To that end, Dr. Smith said that another, stronger piece of supporting evidence that the S. aureus does come from “the crush of human bathers” would be to identify and match isolates from individuals who frequent the beaches with isolates found in sand and water. Dr. Smith said that she and her team are currently seeking funding to carry out these next steps.

The investigators reported no relevant disclosures.

[email protected]

On Twitter @karioakes

BOSTON – Almost half of all sand and water samples taken from Midwestern freshwater public beaches tested positive for Staphylococcus aureus isolates during the summertime, but numbers fell dramatically in the fall and spring.

Overall, according to a study of 10 public beaches in Ohio, almost half of the isolates were resistant to erythromycin, 41% were multidrug resistant, and about 7% were methicillin-resistant S. aureus (MRSA).

In addition, among the 70 S. aureus isolates, 21.4% had the Panton-Valentine leukocidin (PVL) gene, which encodes for a pore-forming toxin identified as a virulence factor in some strains of staphylococcus. The study results were presented by Dipendra Thapaliya, a research associate at Kent State University, Ohio,, during a poster session at the annual meeting of the American Society for Microbiology.

Courtesy Tara Smith

In light of these findings, the study’s senior author, Tara Smith, PhD, professor of epidemiology at the university, said in an interview that beachgoers should take reasonable precautions, including washing lake water and sand off young children upon returning home, and making sure to shower at the beach if facilities are available.

“Staphylococcus does well in a salty environment, but it is a fairly hardy organism,” Dr. Smith said, noting that S. aureus has been found in the sand and water of marine beaches, but it has been less well studied in freshwater environments.

Public beaches in Ohio were the source of the samples. Some sampling was done along the shores of Lake Erie, but smaller inland lakes also were tested, In all, 280 sand and water samples were collected in a 3:1 water to sand ratio.

The samples were incubated and plated for culture and subculture according to established methods, and then tested for S. aureus via catalase and coagulase testing, as well as latex agglutination testing. Isolates were then subjected to antimicrobial susceptibility testing, as well as polymerase chain reaction (PCR) testing for the PVL gene and for the mecA genes found in MRSA. Final isolate identification was achieved by staphylococcal protein A (spa) and multilocus sequence typing.

Of the 27 spa types found from 70 isolates, two common strains, t008 and t002, were the most frequently detected. One livestock-associated strain, t571, was also identified.

Though beaches are frequently contaminated with E. coli and other enteric pathogens, the source is often birds or other wildlife, said Dr. Smith. To try to ascertain the source of the staphylococcus in the summer samples, Mr. Thapaliya and his collaborators repeated testing during the winter months and in the spring, before beachgoers had spent time at the waterside.

Those samples from the months when the beaches were empty of people showed much lower levels of S. aureus: In the summer, S. aureus isolates were found in almost half of the samples obtained (55/120, 45.8%). By contrast, only 5 of the 120 fall samples (4.8%) and 4 of the 40 spring samples (10%) were positive for S. aureus.

“The high prevalence of S. aureus in summer months and presence of human-associated strains may indicate the possible role of human presence in S. aureus contamination in beach water and sand. However, we need further study to confirm such a conclusion,” wrote Mr. Thapaliya and his coauthors.

To that end, Dr. Smith said that another, stronger piece of supporting evidence that the S. aureus does come from “the crush of human bathers” would be to identify and match isolates from individuals who frequent the beaches with isolates found in sand and water. Dr. Smith said that she and her team are currently seeking funding to carry out these next steps.

The investigators reported no relevant disclosures.

[email protected]

On Twitter @karioakes