Bruce Jancin

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas.""The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas.""The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas.""The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

DALLAS – Contrary to expectation, lorazepam and diazepam displayed similar efficacy and safety for treatment of pediatric status epilepticus in a definitive head-to-head randomized controlled trial.

"Both medications are efficacious 70% of the time and both have rates of respiratory depression below 20%. These results contrast with retrospective studies which suggested lorazepam was more effective. The results of our trial suggest that logistic considerations such as need for refrigeration and medication availability rather than concerns about efficacy should influence the choice of benzodiazepine for pediatric status epilepticus," Dr. Jill M. Baren declared at the annual meeting of the Society for Academic Emergency Medicine.

Surveys show that 80% of neurologists have a preference for lorazepam over diazepam on the basis of single-center retrospective studies that reported lorazepam to be more effective in terminating convulsions, with less respiratory depression and a longer duration of action. On the downside, lorazepam, unlike diazepam, is not stable at room temperature. And it is not approved by the Food and Drug Administration for pediatric status epilepticus, so its use there is off label.

Because lorazepam hadn’t been well studied in children, Congress identified it as a high-priority drug in the Best Pharmaceuticals for Children Act. That was the impetus for Dr. Baren and her colleagues in the Pediatric Emergency Care Applied Research Network to conduct their randomized, double-blind, controlled clinical trial involving 273 children and adolescents who presented with convulsive status epilepticus at 14 U.S. and Canadian medical centers. They received either 0.1 mg/kg of IV lorazepam or 0.2 mg/kg of diazepam delivered over a 1-minute push. Half of the initial dose could be repeated at 5 minutes if necessary.

The primary efficacy outcome was cessation of status epilepticus by 10 minutes with no recurrence by 30 minutes. This was achieved in 72.1% of the diazepam group and 72.9% on lorazepam. The primary safety outcome – need for assisted ventilation within 4 hours of giving the study drug – occurred in 16% of the diazepam group and 17.6% of patients on lorazepam, reported Dr. Baren of the University of Pennsylvania, Philadelphia.

Rates of nearly all the prespecified secondary outcomes also were closely similar in the two groups. For example, 62% of patients were successfully treated with a single dose of diazepam, as were 60% on lorazepam. Generalized convulsions recurred within 60 minutes in 11% of the diazepam group and 10% on lorazepam. Response latency averaged 2.5 minutes with diazepam and 2.0 minutes with lorazepam.

Statistically significant differences were seen in only two secondary endpoints. Fifty percent of the diazepam group needed to be placed in deep sedation, compared with 67% of the lorazepam group. And sedation recovery time averaged 104 minutes in the diazepam group versus 120 minutes with lorazepam.

Dr. Baren said that the results of this study, considered together with the findings of the landmark Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), which demonstrated that intramuscular midazolam was comparable in effectiveness to IV lorazepam for pediatric status epilepticus (N. Engl. J. Med. 2012;366:591-600), provide persuasive evidence that any of the three benzodiazepines can be considered acceptable first-line therapy.

"Future research should focus on the development of agents for seizure control in patients with benzodiazepine-refractory seizures and high risk of respiratory failure," she concluded.

Roughly 10,000 children per year in the United States experience status epilepticus. Rapid control is key in order to avoid acute life-threatening complications along with permanent neuronal injury.

This randomized trial was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and carried out by the Pediatric Emergency Care Applied Research Network, which is supported by the Department of Health and Human Services. Dr. Baren reported having no financial conflicts.

bjancin@frontlinemedcom.com

DALLAS – Contrary to expectation, lorazepam and diazepam displayed similar efficacy and safety for treatment of pediatric status epilepticus in a definitive head-to-head randomized controlled trial.

"Both medications are efficacious 70% of the time and both have rates of respiratory depression below 20%. These results contrast with retrospective studies which suggested lorazepam was more effective. The results of our trial suggest that logistic considerations such as need for refrigeration and medication availability rather than concerns about efficacy should influence the choice of benzodiazepine for pediatric status epilepticus," Dr. Jill M. Baren declared at the annual meeting of the Society for Academic Emergency Medicine.

Surveys show that 80% of neurologists have a preference for lorazepam over diazepam on the basis of single-center retrospective studies that reported lorazepam to be more effective in terminating convulsions, with less respiratory depression and a longer duration of action. On the downside, lorazepam, unlike diazepam, is not stable at room temperature. And it is not approved by the Food and Drug Administration for pediatric status epilepticus, so its use there is off label.

Because lorazepam hadn’t been well studied in children, Congress identified it as a high-priority drug in the Best Pharmaceuticals for Children Act. That was the impetus for Dr. Baren and her colleagues in the Pediatric Emergency Care Applied Research Network to conduct their randomized, double-blind, controlled clinical trial involving 273 children and adolescents who presented with convulsive status epilepticus at 14 U.S. and Canadian medical centers. They received either 0.1 mg/kg of IV lorazepam or 0.2 mg/kg of diazepam delivered over a 1-minute push. Half of the initial dose could be repeated at 5 minutes if necessary.

The primary efficacy outcome was cessation of status epilepticus by 10 minutes with no recurrence by 30 minutes. This was achieved in 72.1% of the diazepam group and 72.9% on lorazepam. The primary safety outcome – need for assisted ventilation within 4 hours of giving the study drug – occurred in 16% of the diazepam group and 17.6% of patients on lorazepam, reported Dr. Baren of the University of Pennsylvania, Philadelphia.

Rates of nearly all the prespecified secondary outcomes also were closely similar in the two groups. For example, 62% of patients were successfully treated with a single dose of diazepam, as were 60% on lorazepam. Generalized convulsions recurred within 60 minutes in 11% of the diazepam group and 10% on lorazepam. Response latency averaged 2.5 minutes with diazepam and 2.0 minutes with lorazepam.

Statistically significant differences were seen in only two secondary endpoints. Fifty percent of the diazepam group needed to be placed in deep sedation, compared with 67% of the lorazepam group. And sedation recovery time averaged 104 minutes in the diazepam group versus 120 minutes with lorazepam.

Dr. Baren said that the results of this study, considered together with the findings of the landmark Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), which demonstrated that intramuscular midazolam was comparable in effectiveness to IV lorazepam for pediatric status epilepticus (N. Engl. J. Med. 2012;366:591-600), provide persuasive evidence that any of the three benzodiazepines can be considered acceptable first-line therapy.

"Future research should focus on the development of agents for seizure control in patients with benzodiazepine-refractory seizures and high risk of respiratory failure," she concluded.

Roughly 10,000 children per year in the United States experience status epilepticus. Rapid control is key in order to avoid acute life-threatening complications along with permanent neuronal injury.

This randomized trial was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and carried out by the Pediatric Emergency Care Applied Research Network, which is supported by the Department of Health and Human Services. Dr. Baren reported having no financial conflicts.

bjancin@frontlinemedcom.com

DALLAS – Contrary to expectation, lorazepam and diazepam displayed similar efficacy and safety for treatment of pediatric status epilepticus in a definitive head-to-head randomized controlled trial.

"Both medications are efficacious 70% of the time and both have rates of respiratory depression below 20%. These results contrast with retrospective studies which suggested lorazepam was more effective. The results of our trial suggest that logistic considerations such as need for refrigeration and medication availability rather than concerns about efficacy should influence the choice of benzodiazepine for pediatric status epilepticus," Dr. Jill M. Baren declared at the annual meeting of the Society for Academic Emergency Medicine.

Surveys show that 80% of neurologists have a preference for lorazepam over diazepam on the basis of single-center retrospective studies that reported lorazepam to be more effective in terminating convulsions, with less respiratory depression and a longer duration of action. On the downside, lorazepam, unlike diazepam, is not stable at room temperature. And it is not approved by the Food and Drug Administration for pediatric status epilepticus, so its use there is off label.

Because lorazepam hadn’t been well studied in children, Congress identified it as a high-priority drug in the Best Pharmaceuticals for Children Act. That was the impetus for Dr. Baren and her colleagues in the Pediatric Emergency Care Applied Research Network to conduct their randomized, double-blind, controlled clinical trial involving 273 children and adolescents who presented with convulsive status epilepticus at 14 U.S. and Canadian medical centers. They received either 0.1 mg/kg of IV lorazepam or 0.2 mg/kg of diazepam delivered over a 1-minute push. Half of the initial dose could be repeated at 5 minutes if necessary.

The primary efficacy outcome was cessation of status epilepticus by 10 minutes with no recurrence by 30 minutes. This was achieved in 72.1% of the diazepam group and 72.9% on lorazepam. The primary safety outcome – need for assisted ventilation within 4 hours of giving the study drug – occurred in 16% of the diazepam group and 17.6% of patients on lorazepam, reported Dr. Baren of the University of Pennsylvania, Philadelphia.

Rates of nearly all the prespecified secondary outcomes also were closely similar in the two groups. For example, 62% of patients were successfully treated with a single dose of diazepam, as were 60% on lorazepam. Generalized convulsions recurred within 60 minutes in 11% of the diazepam group and 10% on lorazepam. Response latency averaged 2.5 minutes with diazepam and 2.0 minutes with lorazepam.

Statistically significant differences were seen in only two secondary endpoints. Fifty percent of the diazepam group needed to be placed in deep sedation, compared with 67% of the lorazepam group. And sedation recovery time averaged 104 minutes in the diazepam group versus 120 minutes with lorazepam.

Dr. Baren said that the results of this study, considered together with the findings of the landmark Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), which demonstrated that intramuscular midazolam was comparable in effectiveness to IV lorazepam for pediatric status epilepticus (N. Engl. J. Med. 2012;366:591-600), provide persuasive evidence that any of the three benzodiazepines can be considered acceptable first-line therapy.

"Future research should focus on the development of agents for seizure control in patients with benzodiazepine-refractory seizures and high risk of respiratory failure," she concluded.

Roughly 10,000 children per year in the United States experience status epilepticus. Rapid control is key in order to avoid acute life-threatening complications along with permanent neuronal injury.

This randomized trial was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and carried out by the Pediatric Emergency Care Applied Research Network, which is supported by the Department of Health and Human Services. Dr. Baren reported having no financial conflicts.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.

While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.

It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.

AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.

A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.

A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?

"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.

Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.

Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.

She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.

While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.

It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.

AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.

A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.

A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?

"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.

Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.

Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.

She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.

While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.

It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.

AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.

A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.

A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?

"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.

Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.

Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.

She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.

While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.

It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.

AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.

A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.

A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?

"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.

Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.

Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.

She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.

While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.

It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.

AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.

A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.

A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?

"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.

Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.

Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.

She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Fresh approaches for treating atopic dermatitis are sorely needed, and several intriguing novel therapies are under study, according to Dr. Wynnis Tom.

While topical corticosteroids continue to be the mainstay for control of the inflammation in atopic dermatitis, many patients and families have serious reservations about these medications. Patient concerns persist although, as emphasized in the updated 2014 American Academy of Dermatology guidelines for the management of atopic dermatitis (J. Am. Acad. Dermatol. 2014;70:338-51), these drugs have an excellent risk/benefit ratio when used appropriately.

It’s because of this widespread "steroid phobia" that AN2728 2% ointment is of particular interest, said Dr. Tom, a pediatric dermatologist at Rady Children’s Hospital and the University of California, San Diego.

AN2728 is a boron-based topical phosphodiesterase-4 inhibitor. The boron, she explained, provides added anti-inflammatory effects.

A recent phase I/II open-label, multicenter study involved 34 patients aged 2-17 years with mild to moderate atopic dermatitis and a 25%-35% body surface area of involvement. In this study, twice-daily application of AN2728 for 28 days resulted in 47% of participants achieving "clear" or "almost clear" on investigators’ global assessment, with at least a two-grade improvement from baseline. The affected body surface area plummeted by an average of 78%, while erythema, excoriations, and other symptoms also improved. Only one patient stopped therapy early.

A phase III trial is now in place. The big question relevant to clinical practice is, how does this agent compare in safety and efficacy to topical steroids and topical calcineurin inhibitors?

"We don’t know yet, but it’s nice to see there may be another class of anti-inflammatory agents we may be able to use, especially for those who are worried about topical steroids," Dr. Tom said at the SDEF Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

For the minority of cases of atopic dermatitis that are more severe – and refractory to topical therapies – new agents in clinical trials include the oral phosphodiesterase-4 inhibitor apremilast and dupilumab, a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. Dupilumab, the first biologic agent to undergo evaluation for atopic dermatitis in a formal clinical trial, is now in a phase IIb trial involving adults with moderate to severe disease. Dupilumab is also under study for the treatment of other atopic diseases, including asthma.

Apremilast has been investigated in an open-label, prospective pilot study conducted by dermatologists at Oregon Health and Science University, Portland. The study included 16 adults with moderate to severe atopic dermatitis treated with oral apremilast at 20 or 30 mg b.i.d. for up to 6 months. Participants showed significant improvement on the Eczema Area and Severity Index, the Dermatology Life Quality Index, and other measures (Arch. Dermatol. 2012;148:890-7). Apremilast is approved as Otezla for the treatment of adults with psoriatic arthritis and is under study for other chronic inflammatory diseases, including rheumatoid arthritis and ankylosing spondylitis.

Although to date apremilast and dupilumab have been studied only in adults with atopic dermatitis, dermatologists who treat severely affected children are following the results with interest, because at present their main therapeutic options are heavy-hitting immunosuppressants, Dr. Tom noted.

She reported serving without financial compensation as an investigator for studies funded by Amgen and Anacor, which is developing AN2728 2% ointment. Dr. Tom was a member of the working group responsible for the 2014 AAD guidelines on atopic dermatitis.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Half of patients whose face or scalp actinic keratoses clear completely in response to 3 consecutive days of topical field therapy with ingenol mebutate gel 0.015% will remain clear 12 months later with no further treatment.

That finding from a multicenter prospective study is just one of several recent developments of note in the treatment of actinic keratoses. Other recent studies have addressed the effectiveness of fractional laser therapy and cryotherapy followed by ingenol mebutate, and there have been new developments in phototherapy, Dr. James E. Sligh said in a review of actinic keratosis research at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

• Long-term follow-up of ingenol mebutate therapy. In a multicenter study, dermatologists followed 100 patients with complete clearance of AKs on the face or scalp in response to 3 consecutive days of ingenol mebutate gel (Picato) and 71 patients whose AKs on the trunk or limbs cleared after 2 consecutive days of therapy. The sustained lesion reduction rate, compared with pretreatment baseline was 87.2% for the face and scalp lesions and 86.8% for AKs on the trunk or extremities.

The median time to recurrence was 365 days for AKs on the face and scalp, and shorter at 274 days for lesions on the trunk or extremities, which notably had received 1 less day of treatment. No safety concerns arose during follow-up (JAMA Dermatol. 2013;149:666-70).

• Sequential cryosurgery followed by ingenol mebutate. In a randomized, double-blind, multicenter phase-III trial, 329 patients were randomized to field therapy of AKs on the face or scalp with ingenol mebutate or vehicle 3 weeks after cryosurgery. The complete clearance rate in the treated area at week 11 was significantly higher in the sequential therapy group: 60.5%, compared with 49.4% with cryosurgery alone (J. Drugs Dermatol. 2014;13:154-60).

"I think this is the first in what will be a number of studies where you start to see assessment of combined therapies. But I think the target to look at is not so much what happens at 11 weeks, as in this study, but what happens 1 or 2 years down the road. If you can maintain complete clearance for that long I think it’s worth the extra effort to combine treatment cycles at the beginning," commented Dr. Sligh, chief of the division of dermatology at the University of Arizona, Tucson.

• Laser therapy. Investigators at the Laser and Skin Surgery Center of New York investigated treatment of facial AKs using a fractionated 1927-nm nonablative thulium laser. Twenty-four patients received up to four fractional resurfacing treatments in this prospective trial. At 6 months follow-up, the AK lesion count was down 87%, compared with baseline. Patient satisfaction was high – all participants reported marked or noticeable improvement in overall photodamage – and treatment was well tolerated (J. Am. Acad. Dermatol. 2013;68:98-102).

"If you look at the reduction in AK counts, it stands up very nicely to some of our medical therapies in terms of overall clearance at 6 months, with an 87% reduction – provided you have this special thulium laser in your office," Dr. Sligh observed.

• Photodynamic therapy. What’s new in photodynamic therapy for AKs is not currently available in the United States: methyl aminolevulinate cream 16.8% (Metvixia) for use with red light illumination. This photosensitizer does remain available, however, in Canada and Mexico, according to Dr. Sligh. And aminolevulinic acid (Levulan) is still available as an approved photosensitizer for use with blue light.

"There are many people I know who will activate the Levulan with either a red or blue light source," he said.

Dr. Sligh is on the advisory board for and a consultant to Genentech and has received research grants from DermSpectra and Scibase.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Half of patients whose face or scalp actinic keratoses clear completely in response to 3 consecutive days of topical field therapy with ingenol mebutate gel 0.015% will remain clear 12 months later with no further treatment.

That finding from a multicenter prospective study is just one of several recent developments of note in the treatment of actinic keratoses. Other recent studies have addressed the effectiveness of fractional laser therapy and cryotherapy followed by ingenol mebutate, and there have been new developments in phototherapy, Dr. James E. Sligh said in a review of actinic keratosis research at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

• Long-term follow-up of ingenol mebutate therapy. In a multicenter study, dermatologists followed 100 patients with complete clearance of AKs on the face or scalp in response to 3 consecutive days of ingenol mebutate gel (Picato) and 71 patients whose AKs on the trunk or limbs cleared after 2 consecutive days of therapy. The sustained lesion reduction rate, compared with pretreatment baseline was 87.2% for the face and scalp lesions and 86.8% for AKs on the trunk or extremities.

The median time to recurrence was 365 days for AKs on the face and scalp, and shorter at 274 days for lesions on the trunk or extremities, which notably had received 1 less day of treatment. No safety concerns arose during follow-up (JAMA Dermatol. 2013;149:666-70).

• Sequential cryosurgery followed by ingenol mebutate. In a randomized, double-blind, multicenter phase-III trial, 329 patients were randomized to field therapy of AKs on the face or scalp with ingenol mebutate or vehicle 3 weeks after cryosurgery. The complete clearance rate in the treated area at week 11 was significantly higher in the sequential therapy group: 60.5%, compared with 49.4% with cryosurgery alone (J. Drugs Dermatol. 2014;13:154-60).

"I think this is the first in what will be a number of studies where you start to see assessment of combined therapies. But I think the target to look at is not so much what happens at 11 weeks, as in this study, but what happens 1 or 2 years down the road. If you can maintain complete clearance for that long I think it’s worth the extra effort to combine treatment cycles at the beginning," commented Dr. Sligh, chief of the division of dermatology at the University of Arizona, Tucson.

• Laser therapy. Investigators at the Laser and Skin Surgery Center of New York investigated treatment of facial AKs using a fractionated 1927-nm nonablative thulium laser. Twenty-four patients received up to four fractional resurfacing treatments in this prospective trial. At 6 months follow-up, the AK lesion count was down 87%, compared with baseline. Patient satisfaction was high – all participants reported marked or noticeable improvement in overall photodamage – and treatment was well tolerated (J. Am. Acad. Dermatol. 2013;68:98-102).

"If you look at the reduction in AK counts, it stands up very nicely to some of our medical therapies in terms of overall clearance at 6 months, with an 87% reduction – provided you have this special thulium laser in your office," Dr. Sligh observed.

• Photodynamic therapy. What’s new in photodynamic therapy for AKs is not currently available in the United States: methyl aminolevulinate cream 16.8% (Metvixia) for use with red light illumination. This photosensitizer does remain available, however, in Canada and Mexico, according to Dr. Sligh. And aminolevulinic acid (Levulan) is still available as an approved photosensitizer for use with blue light.

"There are many people I know who will activate the Levulan with either a red or blue light source," he said.

Dr. Sligh is on the advisory board for and a consultant to Genentech and has received research grants from DermSpectra and Scibase.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Half of patients whose face or scalp actinic keratoses clear completely in response to 3 consecutive days of topical field therapy with ingenol mebutate gel 0.015% will remain clear 12 months later with no further treatment.

That finding from a multicenter prospective study is just one of several recent developments of note in the treatment of actinic keratoses. Other recent studies have addressed the effectiveness of fractional laser therapy and cryotherapy followed by ingenol mebutate, and there have been new developments in phototherapy, Dr. James E. Sligh said in a review of actinic keratosis research at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

• Long-term follow-up of ingenol mebutate therapy. In a multicenter study, dermatologists followed 100 patients with complete clearance of AKs on the face or scalp in response to 3 consecutive days of ingenol mebutate gel (Picato) and 71 patients whose AKs on the trunk or limbs cleared after 2 consecutive days of therapy. The sustained lesion reduction rate, compared with pretreatment baseline was 87.2% for the face and scalp lesions and 86.8% for AKs on the trunk or extremities.

The median time to recurrence was 365 days for AKs on the face and scalp, and shorter at 274 days for lesions on the trunk or extremities, which notably had received 1 less day of treatment. No safety concerns arose during follow-up (JAMA Dermatol. 2013;149:666-70).

• Sequential cryosurgery followed by ingenol mebutate. In a randomized, double-blind, multicenter phase-III trial, 329 patients were randomized to field therapy of AKs on the face or scalp with ingenol mebutate or vehicle 3 weeks after cryosurgery. The complete clearance rate in the treated area at week 11 was significantly higher in the sequential therapy group: 60.5%, compared with 49.4% with cryosurgery alone (J. Drugs Dermatol. 2014;13:154-60).

"I think this is the first in what will be a number of studies where you start to see assessment of combined therapies. But I think the target to look at is not so much what happens at 11 weeks, as in this study, but what happens 1 or 2 years down the road. If you can maintain complete clearance for that long I think it’s worth the extra effort to combine treatment cycles at the beginning," commented Dr. Sligh, chief of the division of dermatology at the University of Arizona, Tucson.

• Laser therapy. Investigators at the Laser and Skin Surgery Center of New York investigated treatment of facial AKs using a fractionated 1927-nm nonablative thulium laser. Twenty-four patients received up to four fractional resurfacing treatments in this prospective trial. At 6 months follow-up, the AK lesion count was down 87%, compared with baseline. Patient satisfaction was high – all participants reported marked or noticeable improvement in overall photodamage – and treatment was well tolerated (J. Am. Acad. Dermatol. 2013;68:98-102).

"If you look at the reduction in AK counts, it stands up very nicely to some of our medical therapies in terms of overall clearance at 6 months, with an 87% reduction – provided you have this special thulium laser in your office," Dr. Sligh observed.

• Photodynamic therapy. What’s new in photodynamic therapy for AKs is not currently available in the United States: methyl aminolevulinate cream 16.8% (Metvixia) for use with red light illumination. This photosensitizer does remain available, however, in Canada and Mexico, according to Dr. Sligh. And aminolevulinic acid (Levulan) is still available as an approved photosensitizer for use with blue light.

"There are many people I know who will activate the Levulan with either a red or blue light source," he said.

Dr. Sligh is on the advisory board for and a consultant to Genentech and has received research grants from DermSpectra and Scibase.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

DALLAS – The revised Ottawa Subarachnoid Hemorrhage Rule is now ready for prime-time use in EDs.

The final, tweaked version of the rule sailed through a large new prospective validation study, exhibiting 100% sensitivity and 14% specificity for the detection of this high-mortality headache, Dr. Jeffrey J. Perry reported at the annual meeting of the Society of Academic Emergency Medicine*.

"This tool provides a method to standardize who is investigated in an attempt to minimize the chances of missed diagnosis, given that we know from previous studies that 1 in 20 patients with subarachnoid hemorrhage are missed at the time of their first ED [emergency department] visit," explained Dr. Perry, an emergency physician at the Ottawa Hospital Research Institute and the University of Ottawa.

"The Ottawa Rule will not result in a large reduction in investigations in Canada, but the investigations will be more standardized. I suspect perhaps in the United States, where there’s often a lower threshold to investigate, there may actually be some reduction in investigations, but that hasn’t been assessed," Dr. Perry observed.

An earlier version of the Ottawa Subarachnoid Headache Rule was previously tested in a study conducted at 10 Canadian tertiary-care EDs. In that study, published last year (JAMA 2013;310:1248-55), the rule showed 98.5% sensitivity and 27.5% specificity for subarachnoid hemorrhage (SAH). Dr. Perry and his colleagues felt that 98.5% sensitivity just wasn’t good enough for a condition with 50% mortality and permanent neurologic deficits in 42% of survivors. So they added two additional elements to the rule: "thunderclap headache with instantly peaking pain," and "limited neck flexion on examination." But by changing the Ottawa SAH Rule, it became necessary to conduct a new prospective validation study of the revised rule in a new patient cohort. That’s the study that Dr. Perry presented at SAEM 2014.

The study took place in six Canadian university-affiliated EDs. It included 1,140 patients eligible for application of the rule; that is, they were alert, neurologically intact adults presenting with a new acute nontraumatic headache peaking within 1 hour. They typically reported a pain score of 10 out of a possible 10.

SAH was defined on the basis of subarachnoid blood on a CT scan, RBCs in the final tube of cerebrospinal fluid, or xanthochromia in the cerebrospinal fluid. The SAH diagnostic criteria were met by 64 patients, or 5.6%.

All 64 patients with SAH were identified by the Ottawa SAH Rule as being at high risk for the condition. So were 922 patients who proved not to have SAH. None of the 154 patients identified as low risk by the rule turned out to have SAH. This translated to a rule sensitivity of 100% and specificity of 14.3%. Application of the rule would lead to investigation using CT in 86.5% of patients who presented to the ED with acute headache.

The combined populations of this validation study and the earlier JAMA study totaled 3,271 patients, 196 of whom turned out to have SAH. When the revised rule was applied to the combined cohort, it demonstrated 100% sensitivity and 16.7% specificity for SAH.

Up to 4.5% of all ED visits are for headache. Only 1% of these headaches are SAHs. In the new Ottawa Rule validation study, the largest final diagnostic categories were migraine, which accounted for nearly 20% of the headaches, and benign headache, which was present in 53% and consisted mostly of tension headaches and cluster headaches. Other than SAH, serious headaches were relatively rare, with meningitis the final diagnosis in 0.3% of patients, TIA/stroke in 0.4%, and brain tumor in 0.3%.

The validation study was funded by the Canadian Institutes of Health Research. Dr. Perry reported having no conflicts of interest.

bjancin@frontlinemedcom.com

Correction, 6/23/14: An earlier version of this article misstated the name of the Society of Academic Emergency Medicine.

DALLAS – The revised Ottawa Subarachnoid Hemorrhage Rule is now ready for prime-time use in EDs.

The final, tweaked version of the rule sailed through a large new prospective validation study, exhibiting 100% sensitivity and 14% specificity for the detection of this high-mortality headache, Dr. Jeffrey J. Perry reported at the annual meeting of the Society of Academic Emergency Medicine*.

"This tool provides a method to standardize who is investigated in an attempt to minimize the chances of missed diagnosis, given that we know from previous studies that 1 in 20 patients with subarachnoid hemorrhage are missed at the time of their first ED [emergency department] visit," explained Dr. Perry, an emergency physician at the Ottawa Hospital Research Institute and the University of Ottawa.

"The Ottawa Rule will not result in a large reduction in investigations in Canada, but the investigations will be more standardized. I suspect perhaps in the United States, where there’s often a lower threshold to investigate, there may actually be some reduction in investigations, but that hasn’t been assessed," Dr. Perry observed.

An earlier version of the Ottawa Subarachnoid Headache Rule was previously tested in a study conducted at 10 Canadian tertiary-care EDs. In that study, published last year (JAMA 2013;310:1248-55), the rule showed 98.5% sensitivity and 27.5% specificity for subarachnoid hemorrhage (SAH). Dr. Perry and his colleagues felt that 98.5% sensitivity just wasn’t good enough for a condition with 50% mortality and permanent neurologic deficits in 42% of survivors. So they added two additional elements to the rule: "thunderclap headache with instantly peaking pain," and "limited neck flexion on examination." But by changing the Ottawa SAH Rule, it became necessary to conduct a new prospective validation study of the revised rule in a new patient cohort. That’s the study that Dr. Perry presented at SAEM 2014.

The study took place in six Canadian university-affiliated EDs. It included 1,140 patients eligible for application of the rule; that is, they were alert, neurologically intact adults presenting with a new acute nontraumatic headache peaking within 1 hour. They typically reported a pain score of 10 out of a possible 10.

SAH was defined on the basis of subarachnoid blood on a CT scan, RBCs in the final tube of cerebrospinal fluid, or xanthochromia in the cerebrospinal fluid. The SAH diagnostic criteria were met by 64 patients, or 5.6%.

All 64 patients with SAH were identified by the Ottawa SAH Rule as being at high risk for the condition. So were 922 patients who proved not to have SAH. None of the 154 patients identified as low risk by the rule turned out to have SAH. This translated to a rule sensitivity of 100% and specificity of 14.3%. Application of the rule would lead to investigation using CT in 86.5% of patients who presented to the ED with acute headache.

The combined populations of this validation study and the earlier JAMA study totaled 3,271 patients, 196 of whom turned out to have SAH. When the revised rule was applied to the combined cohort, it demonstrated 100% sensitivity and 16.7% specificity for SAH.

Up to 4.5% of all ED visits are for headache. Only 1% of these headaches are SAHs. In the new Ottawa Rule validation study, the largest final diagnostic categories were migraine, which accounted for nearly 20% of the headaches, and benign headache, which was present in 53% and consisted mostly of tension headaches and cluster headaches. Other than SAH, serious headaches were relatively rare, with meningitis the final diagnosis in 0.3% of patients, TIA/stroke in 0.4%, and brain tumor in 0.3%.

The validation study was funded by the Canadian Institutes of Health Research. Dr. Perry reported having no conflicts of interest.

bjancin@frontlinemedcom.com

Correction, 6/23/14: An earlier version of this article misstated the name of the Society of Academic Emergency Medicine.

DALLAS – The revised Ottawa Subarachnoid Hemorrhage Rule is now ready for prime-time use in EDs.

The final, tweaked version of the rule sailed through a large new prospective validation study, exhibiting 100% sensitivity and 14% specificity for the detection of this high-mortality headache, Dr. Jeffrey J. Perry reported at the annual meeting of the Society of Academic Emergency Medicine*.

"This tool provides a method to standardize who is investigated in an attempt to minimize the chances of missed diagnosis, given that we know from previous studies that 1 in 20 patients with subarachnoid hemorrhage are missed at the time of their first ED [emergency department] visit," explained Dr. Perry, an emergency physician at the Ottawa Hospital Research Institute and the University of Ottawa.

"The Ottawa Rule will not result in a large reduction in investigations in Canada, but the investigations will be more standardized. I suspect perhaps in the United States, where there’s often a lower threshold to investigate, there may actually be some reduction in investigations, but that hasn’t been assessed," Dr. Perry observed.

An earlier version of the Ottawa Subarachnoid Headache Rule was previously tested in a study conducted at 10 Canadian tertiary-care EDs. In that study, published last year (JAMA 2013;310:1248-55), the rule showed 98.5% sensitivity and 27.5% specificity for subarachnoid hemorrhage (SAH). Dr. Perry and his colleagues felt that 98.5% sensitivity just wasn’t good enough for a condition with 50% mortality and permanent neurologic deficits in 42% of survivors. So they added two additional elements to the rule: "thunderclap headache with instantly peaking pain," and "limited neck flexion on examination." But by changing the Ottawa SAH Rule, it became necessary to conduct a new prospective validation study of the revised rule in a new patient cohort. That’s the study that Dr. Perry presented at SAEM 2014.

The study took place in six Canadian university-affiliated EDs. It included 1,140 patients eligible for application of the rule; that is, they were alert, neurologically intact adults presenting with a new acute nontraumatic headache peaking within 1 hour. They typically reported a pain score of 10 out of a possible 10.

SAH was defined on the basis of subarachnoid blood on a CT scan, RBCs in the final tube of cerebrospinal fluid, or xanthochromia in the cerebrospinal fluid. The SAH diagnostic criteria were met by 64 patients, or 5.6%.

All 64 patients with SAH were identified by the Ottawa SAH Rule as being at high risk for the condition. So were 922 patients who proved not to have SAH. None of the 154 patients identified as low risk by the rule turned out to have SAH. This translated to a rule sensitivity of 100% and specificity of 14.3%. Application of the rule would lead to investigation using CT in 86.5% of patients who presented to the ED with acute headache.

The combined populations of this validation study and the earlier JAMA study totaled 3,271 patients, 196 of whom turned out to have SAH. When the revised rule was applied to the combined cohort, it demonstrated 100% sensitivity and 16.7% specificity for SAH.

Up to 4.5% of all ED visits are for headache. Only 1% of these headaches are SAHs. In the new Ottawa Rule validation study, the largest final diagnostic categories were migraine, which accounted for nearly 20% of the headaches, and benign headache, which was present in 53% and consisted mostly of tension headaches and cluster headaches. Other than SAH, serious headaches were relatively rare, with meningitis the final diagnosis in 0.3% of patients, TIA/stroke in 0.4%, and brain tumor in 0.3%.

The validation study was funded by the Canadian Institutes of Health Research. Dr. Perry reported having no conflicts of interest.

bjancin@frontlinemedcom.com

Correction, 6/23/14: An earlier version of this article misstated the name of the Society of Academic Emergency Medicine.

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/Frontline Medical News

"The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas."

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/Frontline Medical News

"The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas."

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The spectacular developments in the treatment of advanced melanoma that began with approval of ipilimumab in 2011 continue to accelerate, and these advances promise to keep dermatologists quite busy for the foreseeable future in treating the cutaneous side effects of these targeted therapies.

Cutaneous toxicities requiring medical attention are extremely common with the new therapeutic agents. The key to minimizing their effects is proactive management, Dr. James E. Sligh emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Bruce Jancin/Frontline Medical News

"The message is that people are living longer with advanced melanoma, but you really need to work with your oncologists to get the absolute benefit patients deserve out of these advanced drugs," he said. "All patients on any of the BRAF inhibitors should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and for 6 months following treatment discontinuation. And while I use this as a guide, there are definitely patients I see for whom 2 months is way too long between visits," he added. "If they’re growing squamous cell carcinomas or verrucous keratoses at a good clip, they need to be seen more often. I’ll see them every other week if need be," said Dr. Sligh, chief of the dermatology division at the University of Arizona, Tucson.

"This is a plea to dermatologists," he continued. "If you have a patient who’s going on a BRAF inhibitor, they need to be seen in your office regularly. And if your next available appointment isn’t until 4 months down the road, you absolutely need to make room for these patients, because after 4 months they may have very large squamous cell carcinomas."

One in four advanced melanoma patients on a BRAF inhibitor – vemurafenib and dabrenafib are the two available thus far – will develop squamous cell carcinomas, Dr. Sligh said. If it’s going to happen, it typically begins in the first month or two of therapy. Caught early, the treatment is simple removal. The same goes for verrucous keratoses, which occur in close to half of treated patients.

"I use cryotherapy in the office, and I give patients 5-FU [5-fluorouracil] so they can start treating a lesion the day they see it, rather than waiting to show it to me a couple of months later," explained Dr. Sligh.

Other common cutaneous adverse events seen as a class effect with the BRAF inhibitors include photosensitivity reactions, seen in approximately one-third of patients in the phase III clinical trials; pruritus, seen in 23%; plantar hyperkeratosis in 10%-20%; and maculopapular rash in 9%.

The pretreatment dermatologic visit is an ideal time for patient education regarding sunscreen use, protective clothing, and the necessity to stay indoors in the event a photosensitivity rash emerges, Dr. Sligh noted. These are issues medical oncologists typically won’t counsel patients about, he said.

"The real advantage to doing this is you want these patients to maintain their optimal dose. For vemurafenib, it’s 960 mg b.i.d. There are very few things that will cause a dose reduction with these drugs, so if cutaneous toxicity is something patients are having a difficult time with, it’s our job as dermatologists to ensure that they have the best chance to make those side effects tolerable. Remaining on the drug is absolutely their best chance for survival," Dr. Sligh continued.

Serious hypersensitivity reactions, including anaphylaxis, as well as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients on a BRAF inhibitor. Such events do require permanent discontinuation of therapy. But that’s not necessarily the end of the road. "There are fantastic new options coming on board each year as alternatives for these people," according to Dr. Sligh.

New primary melanomas can arise while a patient is on BRAF inhibitor therapy. If they are detected early through those bimonthly office visits, the treatment is excision with no dosage adjustment.

Ipilimumab, which targets cytotoxic T-lymphocyte antigen 4, differs from the BRAF inhibitors in that its cutaneous adverse effects can emerge long after the drug is stopped.

"If you see a rash that’s not typical in a patient even 1 or 2 years after they were on ipilimumab, you should still consider that drug to be a likely culprit," Dr. Sligh said.

Trametinib, a MEK inhibitor, was approved last year for the treatment of melanomas with BRAF V600E or V600K mutations. Cutaneous toxicity occurs in close to 90% of patients on the drug, including a 12% rate of severe, grade 3 skin reactions. When trametinib is given in combination with vemurafenib or dabrafenib in an effort to delay emergence of tumor resistance, the result is longer progression-free survival than with either agent alone, and with a lower rate of squamous cell carcinomas and other cutaneous adverse events than with either agent as monotherapy. However, the question of whether or not combination therapy improves overall survival remains unclear, and is the subject of ongoing trials.

Close to half of melanoma patients have a BRAF mutation that makes them a potential candidate for BRAF inhibitor therapy. But in a separate presentation at the meeting, Dr. Michael Postow, an oncologist at Memorial Sloan Kettering Cancer Center in New York, urged dermatologists not to think only of the FDA-approved BRAF test when they have a patient diagnosed with melanoma.

"It’s really worthwhile to do more extensive molecular profiling of those patients, because you may find another targetable mutation," said Dr. Postow. "I would encourage you to refer any patients you have that are being diagnosed with melanoma for a larger institutional evaluation where more extensive molecular characterization of the tumor can be performed," he added.

Dr. Sligh is on the advisory board for and a consultant to Genentech, and he has received research grants from DermSpectra and SciBase. Dr. Postow reported serving as an unpaid adviser to Bristol-Myers Squibb.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

CHICAGO – Infliximab discontinuation rates were lower in a pilot study of inflammatory bowel disease patients who were in remission and had their serum drug levels measured.

Trough infliximab concentrations were measured in patients who were in clinical remission at about 1 year on maintenance therapy. When trough concentrations fell below 5 mcg/mL, patients got a dose increase. The goal was to prevent secondary loss of response due to recurrence of symptoms or antibody-mediated side effects, such as infusion reactions, Dr. Byron P. Vaughn explained at the annual Digestive Disease Week.

In a retrospective, nonrandomized proof-of-concept study, 48 inflammatory bowel disease patients in remission on infliximab were proactively monitored, and 78 matched controls were conventionally managed. The infliximab discontinuation rate during up to 5 years of follow-up was 10% in the proactively monitored group and 31% in the controls. Nearly 90% of treatment discontinuations in the control group were caused by loss of response or development of acute infusion reactions; in contrast, no one in the proactively monitored group stopped infliximab for those reasons.

"We think this is exciting information. We now recommend dose optimization to a trough level of at least 3 mcg/mL, and our current clinical practice is to target a range of 5-10 mcg/mL," said Dr. Vaughn, of Beth Israel Deaconess Medical Center and Harvard University, Boston. Of course, the findings certainly need to be validated in a prospective study, he added.

For about the first year of infliximab therapy, the treatment continuation curves were similar for the two groups. After 1 year, the curves separated and the benefit of proactive trough monitoring could be seen.

The main reasons for stopping infliximab in the control group were a flare of symptoms (15 patients) and acute infusion reactions (6 patients). Neither of these events occurred in the proactively monitored patients. The reasons for treatment discontinuation in the proactively monitored group included drug-induced lupus (1 patient), psoriasis (1 patient), a delayed infusion reaction (1 patient), and a reason unrelated to the medication (1 patient).

Three-quarters of study participants had Crohn’s disease, and the rest had ulcerative colitis. Other investigators have previously shown that an undetectable serum infliximab trough concentration in the setting of Crohn’s disease often heralds a loss of response.

Dr. Vaughn emphasized that fully one in four patients had an undetectable trough level at the first measurement, and nearly two-thirds had levels below 5 mcg/mL. The infliximab dose was increased in those patients. Patients with a trough level of 5-10 mcg/mL received no change in their regimen, while those with a level of more than 10 mcg/mL on two occasions got either a dose reduction or an increase in the interval between doses if they were on 5 mg/kg.

In gastroenterology, serum infliximab concentrations are typically measured when patients stop responding or have side effects. So the costs of proactive infliximab monitoring and dose escalation are going to be an impediment to widespread implementation of this strategy under many health plans, at least until there is confirmatory data, he said.

Proactive trough concentration monitoring and dose titration are typical in recipients of solid organ transplants receiving cyclosporine, mycophenolate mofetil, and mTOR (mammalian target of rapamycin) inhibitors, and are often performed in sepsis patients receiving vancomycin and gentamicin.

When asked how often he recommends proactive infliximab trough testing, Dr. Vaughn replied, "I think when people are in a steady state – they’re not ill and they’re not flaring – you could probably check once every 6 months or maybe once a year. After a few stable troughs, that could be enough unless there’s been a major change like a big weight change, a change in other medications, or an illness."

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

bjancin@frontlinemedcom.com

CHICAGO – Infliximab discontinuation rates were lower in a pilot study of inflammatory bowel disease patients who were in remission and had their serum drug levels measured.

Trough infliximab concentrations were measured in patients who were in clinical remission at about 1 year on maintenance therapy. When trough concentrations fell below 5 mcg/mL, patients got a dose increase. The goal was to prevent secondary loss of response due to recurrence of symptoms or antibody-mediated side effects, such as infusion reactions, Dr. Byron P. Vaughn explained at the annual Digestive Disease Week.

In a retrospective, nonrandomized proof-of-concept study, 48 inflammatory bowel disease patients in remission on infliximab were proactively monitored, and 78 matched controls were conventionally managed. The infliximab discontinuation rate during up to 5 years of follow-up was 10% in the proactively monitored group and 31% in the controls. Nearly 90% of treatment discontinuations in the control group were caused by loss of response or development of acute infusion reactions; in contrast, no one in the proactively monitored group stopped infliximab for those reasons.

"We think this is exciting information. We now recommend dose optimization to a trough level of at least 3 mcg/mL, and our current clinical practice is to target a range of 5-10 mcg/mL," said Dr. Vaughn, of Beth Israel Deaconess Medical Center and Harvard University, Boston. Of course, the findings certainly need to be validated in a prospective study, he added.

For about the first year of infliximab therapy, the treatment continuation curves were similar for the two groups. After 1 year, the curves separated and the benefit of proactive trough monitoring could be seen.

The main reasons for stopping infliximab in the control group were a flare of symptoms (15 patients) and acute infusion reactions (6 patients). Neither of these events occurred in the proactively monitored patients. The reasons for treatment discontinuation in the proactively monitored group included drug-induced lupus (1 patient), psoriasis (1 patient), a delayed infusion reaction (1 patient), and a reason unrelated to the medication (1 patient).

Three-quarters of study participants had Crohn’s disease, and the rest had ulcerative colitis. Other investigators have previously shown that an undetectable serum infliximab trough concentration in the setting of Crohn’s disease often heralds a loss of response.

Dr. Vaughn emphasized that fully one in four patients had an undetectable trough level at the first measurement, and nearly two-thirds had levels below 5 mcg/mL. The infliximab dose was increased in those patients. Patients with a trough level of 5-10 mcg/mL received no change in their regimen, while those with a level of more than 10 mcg/mL on two occasions got either a dose reduction or an increase in the interval between doses if they were on 5 mg/kg.

In gastroenterology, serum infliximab concentrations are typically measured when patients stop responding or have side effects. So the costs of proactive infliximab monitoring and dose escalation are going to be an impediment to widespread implementation of this strategy under many health plans, at least until there is confirmatory data, he said.

Proactive trough concentration monitoring and dose titration are typical in recipients of solid organ transplants receiving cyclosporine, mycophenolate mofetil, and mTOR (mammalian target of rapamycin) inhibitors, and are often performed in sepsis patients receiving vancomycin and gentamicin.

When asked how often he recommends proactive infliximab trough testing, Dr. Vaughn replied, "I think when people are in a steady state – they’re not ill and they’re not flaring – you could probably check once every 6 months or maybe once a year. After a few stable troughs, that could be enough unless there’s been a major change like a big weight change, a change in other medications, or an illness."

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

bjancin@frontlinemedcom.com

CHICAGO – Infliximab discontinuation rates were lower in a pilot study of inflammatory bowel disease patients who were in remission and had their serum drug levels measured.

Trough infliximab concentrations were measured in patients who were in clinical remission at about 1 year on maintenance therapy. When trough concentrations fell below 5 mcg/mL, patients got a dose increase. The goal was to prevent secondary loss of response due to recurrence of symptoms or antibody-mediated side effects, such as infusion reactions, Dr. Byron P. Vaughn explained at the annual Digestive Disease Week.

In a retrospective, nonrandomized proof-of-concept study, 48 inflammatory bowel disease patients in remission on infliximab were proactively monitored, and 78 matched controls were conventionally managed. The infliximab discontinuation rate during up to 5 years of follow-up was 10% in the proactively monitored group and 31% in the controls. Nearly 90% of treatment discontinuations in the control group were caused by loss of response or development of acute infusion reactions; in contrast, no one in the proactively monitored group stopped infliximab for those reasons.

"We think this is exciting information. We now recommend dose optimization to a trough level of at least 3 mcg/mL, and our current clinical practice is to target a range of 5-10 mcg/mL," said Dr. Vaughn, of Beth Israel Deaconess Medical Center and Harvard University, Boston. Of course, the findings certainly need to be validated in a prospective study, he added.

For about the first year of infliximab therapy, the treatment continuation curves were similar for the two groups. After 1 year, the curves separated and the benefit of proactive trough monitoring could be seen.

The main reasons for stopping infliximab in the control group were a flare of symptoms (15 patients) and acute infusion reactions (6 patients). Neither of these events occurred in the proactively monitored patients. The reasons for treatment discontinuation in the proactively monitored group included drug-induced lupus (1 patient), psoriasis (1 patient), a delayed infusion reaction (1 patient), and a reason unrelated to the medication (1 patient).

Three-quarters of study participants had Crohn’s disease, and the rest had ulcerative colitis. Other investigators have previously shown that an undetectable serum infliximab trough concentration in the setting of Crohn’s disease often heralds a loss of response.

Dr. Vaughn emphasized that fully one in four patients had an undetectable trough level at the first measurement, and nearly two-thirds had levels below 5 mcg/mL. The infliximab dose was increased in those patients. Patients with a trough level of 5-10 mcg/mL received no change in their regimen, while those with a level of more than 10 mcg/mL on two occasions got either a dose reduction or an increase in the interval between doses if they were on 5 mg/kg.

In gastroenterology, serum infliximab concentrations are typically measured when patients stop responding or have side effects. So the costs of proactive infliximab monitoring and dose escalation are going to be an impediment to widespread implementation of this strategy under many health plans, at least until there is confirmatory data, he said.

Proactive trough concentration monitoring and dose titration are typical in recipients of solid organ transplants receiving cyclosporine, mycophenolate mofetil, and mTOR (mammalian target of rapamycin) inhibitors, and are often performed in sepsis patients receiving vancomycin and gentamicin.

When asked how often he recommends proactive infliximab trough testing, Dr. Vaughn replied, "I think when people are in a steady state – they’re not ill and they’re not flaring – you could probably check once every 6 months or maybe once a year. After a few stable troughs, that could be enough unless there’s been a major change like a big weight change, a change in other medications, or an illness."

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

bjancin@frontlinemedcom.com

WASHINGTON – A high-intensity cardiac rehabilitation program safely improved quality of life, diastolic function, depressive symptoms, and physical fitness in patients with systolic heart failure and reduced ejection fraction in a randomized controlled trial.

In the subgroup of study participants over age 65, however, the benefits were limited and the dropout rate high, Dr. Christina Chrysohoou said at the annual meeting of the American College of Cardiology. "I think patients over age 65 may benefit more from a less-intensive exercise time and rest periods."

Bruce Jancin/Frontline Medical News

Her study included 100 consecutive patients with a left ventricular ejection fraction (LVEF) below 30%; heart failure of ischemic etiology was present in 70%. One-third of subjects had an implantable cardioverter-defibrillator at study entry. All participants underwent pre-enrollment Holter monitoring with electrophysiologic follow-up as warranted. Participants were randomized to a high-intensity exercise program or to a control arm of standard dietary advice and a recommendation to walk for up to 2 miles daily, said Dr. Chrysohoou, a cardiologist at the University of Athens.

The exercise program consisted of a warm-up followed a 30-minute session of alternating 30-second bursts of ergometric exercise at 100% of a patient’s maximum workload followed by 30 seconds of recovery at 40%-60% of maximum workload. Maximum workload was determined from a baseline treadmill exercise test. The 12-week study was completed by 33 of 50 patients in the high-intensity exercise group and 39 of 50 controls.

Quality of life scores on the Minnesota Living with Heart Failure Questionnaire improved from a mean score of 21 at baseline to 7 in the intensive-exercise group, and declined slightly from 19 to 21 in the control group.

At baseline, the mean score on the Zung Depression Scale was 37 out of a possible 80; at 12 weeks, scores improved to 30 in the high-intensity exercise group and increased to 41 in the controls.

Maximal oxygen consumption, or VO_2max, improved from 16 to 21 mL/kg per minute in the interval-exercise group while remaining unchanged in controls. Similarly, peak power output increased from 84 to 105 W in the exercise program participants while remaining unchanged in controls. Six-minute walk time improved from 422 m to 476 m in the intensive exercisers, a 13% better result than that seen in controls.

Diastolic function on Doppler imaging significantly improved in the exercise group but not in the controls. The E/A wave ratio, which represents the relationship between early passive left ventricular filling and atrial contraction in late diastole, decreased by 24%. Also, the left ventricular outflow velocity integral increased by 4%.

There were no adverse events in either study arm.

LVEF did not significantly improve in either study arm, but that was not surprising, said Dr. Chrysohoou. "You may have an LVEF of 20% and be able to run a marathon, or an LVEF of 30%-35% and not even be able to walk around the house."

This was an unfunded study, and Dr. Chrysohoou reported having no financial conflicts.

bjancin@frontlinemedcom.com

WASHINGTON – A high-intensity cardiac rehabilitation program safely improved quality of life, diastolic function, depressive symptoms, and physical fitness in patients with systolic heart failure and reduced ejection fraction in a randomized controlled trial.

In the subgroup of study participants over age 65, however, the benefits were limited and the dropout rate high, Dr. Christina Chrysohoou said at the annual meeting of the American College of Cardiology. "I think patients over age 65 may benefit more from a less-intensive exercise time and rest periods."

Bruce Jancin/Frontline Medical News

Her study included 100 consecutive patients with a left ventricular ejection fraction (LVEF) below 30%; heart failure of ischemic etiology was present in 70%. One-third of subjects had an implantable cardioverter-defibrillator at study entry. All participants underwent pre-enrollment Holter monitoring with electrophysiologic follow-up as warranted. Participants were randomized to a high-intensity exercise program or to a control arm of standard dietary advice and a recommendation to walk for up to 2 miles daily, said Dr. Chrysohoou, a cardiologist at the University of Athens.

The exercise program consisted of a warm-up followed a 30-minute session of alternating 30-second bursts of ergometric exercise at 100% of a patient’s maximum workload followed by 30 seconds of recovery at 40%-60% of maximum workload. Maximum workload was determined from a baseline treadmill exercise test. The 12-week study was completed by 33 of 50 patients in the high-intensity exercise group and 39 of 50 controls.

Quality of life scores on the Minnesota Living with Heart Failure Questionnaire improved from a mean score of 21 at baseline to 7 in the intensive-exercise group, and declined slightly from 19 to 21 in the control group.

At baseline, the mean score on the Zung Depression Scale was 37 out of a possible 80; at 12 weeks, scores improved to 30 in the high-intensity exercise group and increased to 41 in the controls.

Maximal oxygen consumption, or VO_2max, improved from 16 to 21 mL/kg per minute in the interval-exercise group while remaining unchanged in controls. Similarly, peak power output increased from 84 to 105 W in the exercise program participants while remaining unchanged in controls. Six-minute walk time improved from 422 m to 476 m in the intensive exercisers, a 13% better result than that seen in controls.

Diastolic function on Doppler imaging significantly improved in the exercise group but not in the controls. The E/A wave ratio, which represents the relationship between early passive left ventricular filling and atrial contraction in late diastole, decreased by 24%. Also, the left ventricular outflow velocity integral increased by 4%.

There were no adverse events in either study arm.

LVEF did not significantly improve in either study arm, but that was not surprising, said Dr. Chrysohoou. "You may have an LVEF of 20% and be able to run a marathon, or an LVEF of 30%-35% and not even be able to walk around the house."

This was an unfunded study, and Dr. Chrysohoou reported having no financial conflicts.

bjancin@frontlinemedcom.com

WASHINGTON – A high-intensity cardiac rehabilitation program safely improved quality of life, diastolic function, depressive symptoms, and physical fitness in patients with systolic heart failure and reduced ejection fraction in a randomized controlled trial.

In the subgroup of study participants over age 65, however, the benefits were limited and the dropout rate high, Dr. Christina Chrysohoou said at the annual meeting of the American College of Cardiology. "I think patients over age 65 may benefit more from a less-intensive exercise time and rest periods."

Bruce Jancin/Frontline Medical News

Her study included 100 consecutive patients with a left ventricular ejection fraction (LVEF) below 30%; heart failure of ischemic etiology was present in 70%. One-third of subjects had an implantable cardioverter-defibrillator at study entry. All participants underwent pre-enrollment Holter monitoring with electrophysiologic follow-up as warranted. Participants were randomized to a high-intensity exercise program or to a control arm of standard dietary advice and a recommendation to walk for up to 2 miles daily, said Dr. Chrysohoou, a cardiologist at the University of Athens.

The exercise program consisted of a warm-up followed a 30-minute session of alternating 30-second bursts of ergometric exercise at 100% of a patient’s maximum workload followed by 30 seconds of recovery at 40%-60% of maximum workload. Maximum workload was determined from a baseline treadmill exercise test. The 12-week study was completed by 33 of 50 patients in the high-intensity exercise group and 39 of 50 controls.

Quality of life scores on the Minnesota Living with Heart Failure Questionnaire improved from a mean score of 21 at baseline to 7 in the intensive-exercise group, and declined slightly from 19 to 21 in the control group.

At baseline, the mean score on the Zung Depression Scale was 37 out of a possible 80; at 12 weeks, scores improved to 30 in the high-intensity exercise group and increased to 41 in the controls.

Maximal oxygen consumption, or VO_2max, improved from 16 to 21 mL/kg per minute in the interval-exercise group while remaining unchanged in controls. Similarly, peak power output increased from 84 to 105 W in the exercise program participants while remaining unchanged in controls. Six-minute walk time improved from 422 m to 476 m in the intensive exercisers, a 13% better result than that seen in controls.

Diastolic function on Doppler imaging significantly improved in the exercise group but not in the controls. The E/A wave ratio, which represents the relationship between early passive left ventricular filling and atrial contraction in late diastole, decreased by 24%. Also, the left ventricular outflow velocity integral increased by 4%.

There were no adverse events in either study arm.

LVEF did not significantly improve in either study arm, but that was not surprising, said Dr. Chrysohoou. "You may have an LVEF of 20% and be able to run a marathon, or an LVEF of 30%-35% and not even be able to walk around the house."

This was an unfunded study, and Dr. Chrysohoou reported having no financial conflicts.

bjancin@frontlinemedcom.com

LAS VEGAS – Seventeen percent of severely obese adolescents slated for bariatric surgery in the Teen-Longitudinal Assessment of Bariatric Surgery study already had micro- or macroalbuminuria.

At a meeting sponsored by the National Kidney Foundation, Dr. Nianzhou Xiao said that future reports from the ongoing Teen-LABS study will provide the answer to a critical question: Is this worrisome loss of kidney function so early in life reversible via surgical weight loss?

Dr. Xiao presented a cross-sectional baseline report on 242 severely obese adolescents with a median body mass index of 50.5 kg/m². Fourteen percent had microalbuminuria and another 3.1% had macroalbuminuria. Although the group’s mean estimated glomerular filtration rate was 107.6 mL/min per 1.73 m², 3% of the teens had an eGFR below 60 mL/min 1.73 m², which is the definition of stage 3 chronic kidney disease.

In addition, 45% of the teens were hypertensive before surgery, 74% were dyslipidemic, and 13.6% had diabetes. The group’s median serum ferritin was 37 mcg/L, noted Dr. Xiao of Cincinnati Children’s Hospital Medical Center.

Multivariate analysis identified two independent risk factors for an elevated albumin to creatinine ratio: female gender, with an associated 2.34-fold increased risk, and elevated serum ferritin. For every 10 mcg/L of ferritin, the likelihood of an elevated albumin-to-creatinine ratio rose by 7%.

An estimated 4%-6% of U.S. children and adolescents are severely obese, defined as a body mass index of 35 kg/m² or more or a body weight above the 120th percentile. The ongoing Teen-LABS study is the most comprehensive examination of kidney status in severely obese adolescents undergoing bariatric surgery.

Teen-LABS is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Xiao reported having no financial conflicts.

bjancin@frontlinemedcom.com

LAS VEGAS – Seventeen percent of severely obese adolescents slated for bariatric surgery in the Teen-Longitudinal Assessment of Bariatric Surgery study already had micro- or macroalbuminuria.

At a meeting sponsored by the National Kidney Foundation, Dr. Nianzhou Xiao said that future reports from the ongoing Teen-LABS study will provide the answer to a critical question: Is this worrisome loss of kidney function so early in life reversible via surgical weight loss?

Dr. Xiao presented a cross-sectional baseline report on 242 severely obese adolescents with a median body mass index of 50.5 kg/m². Fourteen percent had microalbuminuria and another 3.1% had macroalbuminuria. Although the group’s mean estimated glomerular filtration rate was 107.6 mL/min per 1.73 m², 3% of the teens had an eGFR below 60 mL/min 1.73 m², which is the definition of stage 3 chronic kidney disease.

In addition, 45% of the teens were hypertensive before surgery, 74% were dyslipidemic, and 13.6% had diabetes. The group’s median serum ferritin was 37 mcg/L, noted Dr. Xiao of Cincinnati Children’s Hospital Medical Center.

Multivariate analysis identified two independent risk factors for an elevated albumin to creatinine ratio: female gender, with an associated 2.34-fold increased risk, and elevated serum ferritin. For every 10 mcg/L of ferritin, the likelihood of an elevated albumin-to-creatinine ratio rose by 7%.

An estimated 4%-6% of U.S. children and adolescents are severely obese, defined as a body mass index of 35 kg/m² or more or a body weight above the 120th percentile. The ongoing Teen-LABS study is the most comprehensive examination of kidney status in severely obese adolescents undergoing bariatric surgery.

Teen-LABS is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Xiao reported having no financial conflicts.

bjancin@frontlinemedcom.com

LAS VEGAS – Seventeen percent of severely obese adolescents slated for bariatric surgery in the Teen-Longitudinal Assessment of Bariatric Surgery study already had micro- or macroalbuminuria.

At a meeting sponsored by the National Kidney Foundation, Dr. Nianzhou Xiao said that future reports from the ongoing Teen-LABS study will provide the answer to a critical question: Is this worrisome loss of kidney function so early in life reversible via surgical weight loss?

Dr. Xiao presented a cross-sectional baseline report on 242 severely obese adolescents with a median body mass index of 50.5 kg/m². Fourteen percent had microalbuminuria and another 3.1% had macroalbuminuria. Although the group’s mean estimated glomerular filtration rate was 107.6 mL/min per 1.73 m², 3% of the teens had an eGFR below 60 mL/min 1.73 m², which is the definition of stage 3 chronic kidney disease.

In addition, 45% of the teens were hypertensive before surgery, 74% were dyslipidemic, and 13.6% had diabetes. The group’s median serum ferritin was 37 mcg/L, noted Dr. Xiao of Cincinnati Children’s Hospital Medical Center.

Multivariate analysis identified two independent risk factors for an elevated albumin to creatinine ratio: female gender, with an associated 2.34-fold increased risk, and elevated serum ferritin. For every 10 mcg/L of ferritin, the likelihood of an elevated albumin-to-creatinine ratio rose by 7%.

An estimated 4%-6% of U.S. children and adolescents are severely obese, defined as a body mass index of 35 kg/m² or more or a body weight above the 120th percentile. The ongoing Teen-LABS study is the most comprehensive examination of kidney status in severely obese adolescents undergoing bariatric surgery.

Teen-LABS is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Xiao reported having no financial conflicts.

bjancin@frontlinemedcom.com