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Chemoprevention: Thinking outside the box
WAILEA, HAWAII – Nicotinamide is one of the rare proposed agents for skin cancer chemoprevention distinguished by dirt cheap cost combined with a highly reassuring safety profile plus evidence of efficacy – which, together, make it a reasonable option in high risk patients, according to Daniel M. Siegel, MD.
Other agents that fit into that category include the tropical rainforest fern Polypodium leucotomos and milk thistle, added Dr. Siegel, a dermatologist at the State University of New York, Brooklyn.
“That’s a really interesting one. I don’t know if, 5 years from now, we’ll all be taking low-dose rapamycin as an antiaging drug, but we might, especially if someone figures out the ideal dose,” he said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
Nicotinamide
In the case of nicotinamide, the efficacy is actually supported by published level 1 evidence in the form of a highly positive 1-year, double-blind, randomized, placebo-controlled phase III clinical trial.
“You can Google ‘nicotinamide’ and find it at places like Costco and Trader Joe’s for less than 6 cents per day. That makes for a really good risk/benefit ratio. A nickel a day: That’s a cheap one. That’s one where I’d say, ‘Why not?’ It seems to be safe,” Dr. Siegel said.
In the phase III ONTRAC trial, Australian investigators randomized 386 patients who averaged roughly eight nonmelanoma skin cancers in the past 5 years to either 500 mg of oral nicotinamide twice daily or matched placebo for 12 months. During the study period, the nicotinamide group had a statistically significant and clinically meaningful 23% reduction in new nonmelanoma skin cancers, compared with the control group. They also had 13% fewer actinic keratoses at 12 months than controls. And the side effect profile mirrored that of placebo (N Engl J Med. 2015 Oct 22;373[17]:1618-26).
“Nicotinamide is vitamin B3. It’s not niacin. It doesn’t cause flushing and other vasodilatory effects. It’s actually pretty innocuous,” Dr. Siegel said.
In laboratory studies, nicotinamide has been shown to enhance DNA repair following UV exposure, as well as curb UV-induced immunosuppression.
Polypodium leucotomos Samambaia
This plant, commonly known as calaguala in the Spanish-speaking tropics and samambaia in Brazil, has a centuries-long tradition of safe medicinal use. It is commercially available over-the-counter (OTC) as a standardized product called Heliocare, designed to avoid the guesswork involved in topical sunscreen application. Each capsule contains 240 mg of an extract of P. leucotomos. Dr. Siegel said he takes it daily when he’s in a sunny locale, such as Hawaii.
Milk thistle
This plant, known as Silybum marianum, has silymarin as its bioactive compound. Dermatologist Haines Ely, MD, of the University of California, Davis, has reported therapeutic success using it in porphyria cutanea tarda and other conditions. It has been shown to inhibit photocarcinogenesis in animal studies.
Dr. Siegel said that, while Dr. Ely has told him his preferred preparation is a German OTC product, milk thistle seeds can be found in health food stores, ground to a powder using a coffee bean grinder, and used as a food supplement. Like Polypodium leucotomos and nicotinamide, milk thistle is nontoxic.
Rapamycin
This macrolide compound is produced by the bacterium Streptomyces hygroscopicus. Rapamycin is an immunosuppressant used to coat coronary stents and prevent rejection of transplanted organs. It is an mechanistic target of rapamycin signaling pathway inhibitor being studied as a cancer prevention and antiaging agent.
Science magazine called the discovery that rapamycin increased the lifespan of mice one of the top scientific breakthroughs of 2009. Subsequent animal studies have established that the extended lifespan wasn’t solely the result of rapamycin’s antineoplastic effects but of across-the-board delayed onset of all the major age-related diseases. Thus, rapamycin could turn out to be a true antiaging agent, in Dr. Siegel’s view.
Studies in humans are underway. Researchers at Novartis have reported that a rapamycin-related compound curbed the typical decline in immune function that accompanies aging as reflected in a 20% enhancement in the response to influenza vaccine in elderly volunteers (Sci Transl Med. 2014 Dec 24;6[268]:268ra179).
Dr. Siegel reported serving as a consultant to Ferndale, which markets Heliocare. The SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – Nicotinamide is one of the rare proposed agents for skin cancer chemoprevention distinguished by dirt cheap cost combined with a highly reassuring safety profile plus evidence of efficacy – which, together, make it a reasonable option in high risk patients, according to Daniel M. Siegel, MD.
Other agents that fit into that category include the tropical rainforest fern Polypodium leucotomos and milk thistle, added Dr. Siegel, a dermatologist at the State University of New York, Brooklyn.
“That’s a really interesting one. I don’t know if, 5 years from now, we’ll all be taking low-dose rapamycin as an antiaging drug, but we might, especially if someone figures out the ideal dose,” he said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
Nicotinamide
In the case of nicotinamide, the efficacy is actually supported by published level 1 evidence in the form of a highly positive 1-year, double-blind, randomized, placebo-controlled phase III clinical trial.
“You can Google ‘nicotinamide’ and find it at places like Costco and Trader Joe’s for less than 6 cents per day. That makes for a really good risk/benefit ratio. A nickel a day: That’s a cheap one. That’s one where I’d say, ‘Why not?’ It seems to be safe,” Dr. Siegel said.
In the phase III ONTRAC trial, Australian investigators randomized 386 patients who averaged roughly eight nonmelanoma skin cancers in the past 5 years to either 500 mg of oral nicotinamide twice daily or matched placebo for 12 months. During the study period, the nicotinamide group had a statistically significant and clinically meaningful 23% reduction in new nonmelanoma skin cancers, compared with the control group. They also had 13% fewer actinic keratoses at 12 months than controls. And the side effect profile mirrored that of placebo (N Engl J Med. 2015 Oct 22;373[17]:1618-26).
“Nicotinamide is vitamin B3. It’s not niacin. It doesn’t cause flushing and other vasodilatory effects. It’s actually pretty innocuous,” Dr. Siegel said.
In laboratory studies, nicotinamide has been shown to enhance DNA repair following UV exposure, as well as curb UV-induced immunosuppression.
Polypodium leucotomos Samambaia
This plant, commonly known as calaguala in the Spanish-speaking tropics and samambaia in Brazil, has a centuries-long tradition of safe medicinal use. It is commercially available over-the-counter (OTC) as a standardized product called Heliocare, designed to avoid the guesswork involved in topical sunscreen application. Each capsule contains 240 mg of an extract of P. leucotomos. Dr. Siegel said he takes it daily when he’s in a sunny locale, such as Hawaii.
Milk thistle
This plant, known as Silybum marianum, has silymarin as its bioactive compound. Dermatologist Haines Ely, MD, of the University of California, Davis, has reported therapeutic success using it in porphyria cutanea tarda and other conditions. It has been shown to inhibit photocarcinogenesis in animal studies.
Dr. Siegel said that, while Dr. Ely has told him his preferred preparation is a German OTC product, milk thistle seeds can be found in health food stores, ground to a powder using a coffee bean grinder, and used as a food supplement. Like Polypodium leucotomos and nicotinamide, milk thistle is nontoxic.
Rapamycin
This macrolide compound is produced by the bacterium Streptomyces hygroscopicus. Rapamycin is an immunosuppressant used to coat coronary stents and prevent rejection of transplanted organs. It is an mechanistic target of rapamycin signaling pathway inhibitor being studied as a cancer prevention and antiaging agent.
Science magazine called the discovery that rapamycin increased the lifespan of mice one of the top scientific breakthroughs of 2009. Subsequent animal studies have established that the extended lifespan wasn’t solely the result of rapamycin’s antineoplastic effects but of across-the-board delayed onset of all the major age-related diseases. Thus, rapamycin could turn out to be a true antiaging agent, in Dr. Siegel’s view.
Studies in humans are underway. Researchers at Novartis have reported that a rapamycin-related compound curbed the typical decline in immune function that accompanies aging as reflected in a 20% enhancement in the response to influenza vaccine in elderly volunteers (Sci Transl Med. 2014 Dec 24;6[268]:268ra179).
Dr. Siegel reported serving as a consultant to Ferndale, which markets Heliocare. The SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – Nicotinamide is one of the rare proposed agents for skin cancer chemoprevention distinguished by dirt cheap cost combined with a highly reassuring safety profile plus evidence of efficacy – which, together, make it a reasonable option in high risk patients, according to Daniel M. Siegel, MD.
Other agents that fit into that category include the tropical rainforest fern Polypodium leucotomos and milk thistle, added Dr. Siegel, a dermatologist at the State University of New York, Brooklyn.
“That’s a really interesting one. I don’t know if, 5 years from now, we’ll all be taking low-dose rapamycin as an antiaging drug, but we might, especially if someone figures out the ideal dose,” he said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
Nicotinamide
In the case of nicotinamide, the efficacy is actually supported by published level 1 evidence in the form of a highly positive 1-year, double-blind, randomized, placebo-controlled phase III clinical trial.
“You can Google ‘nicotinamide’ and find it at places like Costco and Trader Joe’s for less than 6 cents per day. That makes for a really good risk/benefit ratio. A nickel a day: That’s a cheap one. That’s one where I’d say, ‘Why not?’ It seems to be safe,” Dr. Siegel said.
In the phase III ONTRAC trial, Australian investigators randomized 386 patients who averaged roughly eight nonmelanoma skin cancers in the past 5 years to either 500 mg of oral nicotinamide twice daily or matched placebo for 12 months. During the study period, the nicotinamide group had a statistically significant and clinically meaningful 23% reduction in new nonmelanoma skin cancers, compared with the control group. They also had 13% fewer actinic keratoses at 12 months than controls. And the side effect profile mirrored that of placebo (N Engl J Med. 2015 Oct 22;373[17]:1618-26).
“Nicotinamide is vitamin B3. It’s not niacin. It doesn’t cause flushing and other vasodilatory effects. It’s actually pretty innocuous,” Dr. Siegel said.
In laboratory studies, nicotinamide has been shown to enhance DNA repair following UV exposure, as well as curb UV-induced immunosuppression.
Polypodium leucotomos Samambaia
This plant, commonly known as calaguala in the Spanish-speaking tropics and samambaia in Brazil, has a centuries-long tradition of safe medicinal use. It is commercially available over-the-counter (OTC) as a standardized product called Heliocare, designed to avoid the guesswork involved in topical sunscreen application. Each capsule contains 240 mg of an extract of P. leucotomos. Dr. Siegel said he takes it daily when he’s in a sunny locale, such as Hawaii.
Milk thistle
This plant, known as Silybum marianum, has silymarin as its bioactive compound. Dermatologist Haines Ely, MD, of the University of California, Davis, has reported therapeutic success using it in porphyria cutanea tarda and other conditions. It has been shown to inhibit photocarcinogenesis in animal studies.
Dr. Siegel said that, while Dr. Ely has told him his preferred preparation is a German OTC product, milk thistle seeds can be found in health food stores, ground to a powder using a coffee bean grinder, and used as a food supplement. Like Polypodium leucotomos and nicotinamide, milk thistle is nontoxic.
Rapamycin
This macrolide compound is produced by the bacterium Streptomyces hygroscopicus. Rapamycin is an immunosuppressant used to coat coronary stents and prevent rejection of transplanted organs. It is an mechanistic target of rapamycin signaling pathway inhibitor being studied as a cancer prevention and antiaging agent.
Science magazine called the discovery that rapamycin increased the lifespan of mice one of the top scientific breakthroughs of 2009. Subsequent animal studies have established that the extended lifespan wasn’t solely the result of rapamycin’s antineoplastic effects but of across-the-board delayed onset of all the major age-related diseases. Thus, rapamycin could turn out to be a true antiaging agent, in Dr. Siegel’s view.
Studies in humans are underway. Researchers at Novartis have reported that a rapamycin-related compound curbed the typical decline in immune function that accompanies aging as reflected in a 20% enhancement in the response to influenza vaccine in elderly volunteers (Sci Transl Med. 2014 Dec 24;6[268]:268ra179).
Dr. Siegel reported serving as a consultant to Ferndale, which markets Heliocare. The SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Know your new hyaluronic acid–based fillers
WAILEA, HAWAII – American dermatologists are now gaining access to a lot of new hyaluronic acid-based fillers, designed to address limitations in the older, tried-and-true product lines, according to Nowell Solish, MD.
These products have been available in Canada for years. Dr. Solish, a dermatologist at the University of Toronto, shared insights regarding their optimal use, based on his extensive experience with them.
Allergan’s earlier Juvéderm Ultra range of dermal fillers is based on Hylacross, which utilizes crosslinked high–molecular weight HA.
“These products have been around a long time and have lots of benefits, but there were definitely some things missing in the product line,” he explained. “We wanted more control of gel swelling – that is, how much water the hyaluronic acid takes up.”
The Vycross technology employs a proprietary mix of low– and high–molecular weight HA, which results in a highly crosslinked gel that’s moldable immediately after injection, displays minimal gel swelling, and is designed to last longer than earlier-generation fillers.
The main difference between the three products lies in their HA concentrations: Juvéderm Voluma XC has the highest concentration of HA and Juvéderm Volbella XC the lowest, with Volift in between.
The company claims that outcomes with Volbella and Volift last up to 12 months, while Voluma outcomes lasts for up to 24 months. Dr. Solish suggested that his American colleagues take that with a grain of salt.
“I would say I always underpromise and overdeliver with my patients,” he noted. “I think you can probably detect Voluma at 2 years, but, the question is, how good is the effect? How happy is the patient? I think 2 years is a little bit of a stretch. I think it lasts for about 9 months to a year before reinjection.”
Voluma has been available in the United States for several years, while Dr. Solish has been using it far longer. His impression is that Voluma is great for creating volume, especially in the cheeks, midface, and submalar area. He finds that he gets his best results by implanting the product in a series of small, 0.2-mL, tent-like boluses. The reinjection volume is typically substantially less than that employed in initial treatment.
Volbella received approval from the FDA in autumn 2016 for perioral injection and is just now reaching the U.S. marketplace.
“In my humble opinion, I don’t think Volbella is really good for volume,” he explained. “I think it’s great for what I call lip hydration, to give that lip a lipstick look. Where I find that I use this product the most is for the perioral rhytids – the vertical lip lines people sometimes call smokers’ lines. I implant it in the lip mucosa to straighten out the folds.”
Dr. Solish cautioned that Volbella is a fast-flowing product.
“The thing you have to be careful about with Volbella is it has a very low extrusion force,” he noted. “That means it’s very easy to unload the syringe and get too much product out. And there’s no question that there’s a direct correlation between speed of injection and adverse events, mainly edema. So, just remember to slow your hand down, or off-label to add a 31- or even 32-gauge needle to the syringe.”
Volift is not yet approved in the United States, but it’s coming. Dr. Solish called it “a good workhorse product” for mild-to-moderate lines around the face.
“Sales will be much higher than for Volbella, because Volift is great for the in-between things,” the dermatologist continued. “You have Voluma for volume on the midface and cheeks, but Volift is great for nasolabial folds and, especially, for marionette lines and smile lines, where you don’t want a lot of bulk.”
The main adverse event encountered with any of the three products is delayed-onset development of nonpainful inflammatory nodules arising 3-6 months post injection. In one Canadian study, the incidence was less than 0.5% (Dermatol Surg. 2015 Sep;41[9]:1060-7).
Dr. Solish recommended treating the nodules with weekly or biweekly intralesional injections of hyaluronidase, followed by intralesional injections of 0.1 mL/cm2 of triamcinolone (Kenalog) at 2.5 mg/mL to 5.0 mg/mL.
Turning to Galderma’s NASHA technology, Dr. Solish explained that it relies on naturally occurring entanglement of HA chains to create gel particles formulated at 20 mg/dL. By varying the gel particle size and the amount of crosslinking, the company has created a series of products with different properties.
Restylane Refyne features smaller-size particles and less crosslinking, which makes for a softer gel. It’s an excellent option for marionette lines, mild nasolabial folds, and small perioral lines, and “it’s my absolute go-to for tear troughs,” Dr. Solish said.
In contrast, Restylane Defyne has bigger gel particles and more extensive HA crosslinking. It is firmer than Refyne and is best suited for achieving lift and volume. He implants it in the cheeks, forehead, temples, and deeper nasolabial folds.
In addition to these two products, which are new to the United States, Galderma has rebranded Perlane as Restylane Lyft, approved for midfacial augmentation. Another product, Restylane Silk, is similar to Volbella in that it is fast-flowing and not a big volumizer. Dr. Solish called it “lipstick in a syringe,” best suited for improving definition of the lips and for addressing perioral fine lines.
Dr. Solish reported serving as an investigator and/or consultant for Allergan, Galderma, Indeed, Merz, Revance Therapeutics, and Valeant. The SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – American dermatologists are now gaining access to a lot of new hyaluronic acid-based fillers, designed to address limitations in the older, tried-and-true product lines, according to Nowell Solish, MD.
These products have been available in Canada for years. Dr. Solish, a dermatologist at the University of Toronto, shared insights regarding their optimal use, based on his extensive experience with them.
Allergan’s earlier Juvéderm Ultra range of dermal fillers is based on Hylacross, which utilizes crosslinked high–molecular weight HA.
“These products have been around a long time and have lots of benefits, but there were definitely some things missing in the product line,” he explained. “We wanted more control of gel swelling – that is, how much water the hyaluronic acid takes up.”
The Vycross technology employs a proprietary mix of low– and high–molecular weight HA, which results in a highly crosslinked gel that’s moldable immediately after injection, displays minimal gel swelling, and is designed to last longer than earlier-generation fillers.
The main difference between the three products lies in their HA concentrations: Juvéderm Voluma XC has the highest concentration of HA and Juvéderm Volbella XC the lowest, with Volift in between.
The company claims that outcomes with Volbella and Volift last up to 12 months, while Voluma outcomes lasts for up to 24 months. Dr. Solish suggested that his American colleagues take that with a grain of salt.
“I would say I always underpromise and overdeliver with my patients,” he noted. “I think you can probably detect Voluma at 2 years, but, the question is, how good is the effect? How happy is the patient? I think 2 years is a little bit of a stretch. I think it lasts for about 9 months to a year before reinjection.”
Voluma has been available in the United States for several years, while Dr. Solish has been using it far longer. His impression is that Voluma is great for creating volume, especially in the cheeks, midface, and submalar area. He finds that he gets his best results by implanting the product in a series of small, 0.2-mL, tent-like boluses. The reinjection volume is typically substantially less than that employed in initial treatment.
Volbella received approval from the FDA in autumn 2016 for perioral injection and is just now reaching the U.S. marketplace.
“In my humble opinion, I don’t think Volbella is really good for volume,” he explained. “I think it’s great for what I call lip hydration, to give that lip a lipstick look. Where I find that I use this product the most is for the perioral rhytids – the vertical lip lines people sometimes call smokers’ lines. I implant it in the lip mucosa to straighten out the folds.”
Dr. Solish cautioned that Volbella is a fast-flowing product.
“The thing you have to be careful about with Volbella is it has a very low extrusion force,” he noted. “That means it’s very easy to unload the syringe and get too much product out. And there’s no question that there’s a direct correlation between speed of injection and adverse events, mainly edema. So, just remember to slow your hand down, or off-label to add a 31- or even 32-gauge needle to the syringe.”
Volift is not yet approved in the United States, but it’s coming. Dr. Solish called it “a good workhorse product” for mild-to-moderate lines around the face.
“Sales will be much higher than for Volbella, because Volift is great for the in-between things,” the dermatologist continued. “You have Voluma for volume on the midface and cheeks, but Volift is great for nasolabial folds and, especially, for marionette lines and smile lines, where you don’t want a lot of bulk.”
The main adverse event encountered with any of the three products is delayed-onset development of nonpainful inflammatory nodules arising 3-6 months post injection. In one Canadian study, the incidence was less than 0.5% (Dermatol Surg. 2015 Sep;41[9]:1060-7).
Dr. Solish recommended treating the nodules with weekly or biweekly intralesional injections of hyaluronidase, followed by intralesional injections of 0.1 mL/cm2 of triamcinolone (Kenalog) at 2.5 mg/mL to 5.0 mg/mL.
Turning to Galderma’s NASHA technology, Dr. Solish explained that it relies on naturally occurring entanglement of HA chains to create gel particles formulated at 20 mg/dL. By varying the gel particle size and the amount of crosslinking, the company has created a series of products with different properties.
Restylane Refyne features smaller-size particles and less crosslinking, which makes for a softer gel. It’s an excellent option for marionette lines, mild nasolabial folds, and small perioral lines, and “it’s my absolute go-to for tear troughs,” Dr. Solish said.
In contrast, Restylane Defyne has bigger gel particles and more extensive HA crosslinking. It is firmer than Refyne and is best suited for achieving lift and volume. He implants it in the cheeks, forehead, temples, and deeper nasolabial folds.
In addition to these two products, which are new to the United States, Galderma has rebranded Perlane as Restylane Lyft, approved for midfacial augmentation. Another product, Restylane Silk, is similar to Volbella in that it is fast-flowing and not a big volumizer. Dr. Solish called it “lipstick in a syringe,” best suited for improving definition of the lips and for addressing perioral fine lines.
Dr. Solish reported serving as an investigator and/or consultant for Allergan, Galderma, Indeed, Merz, Revance Therapeutics, and Valeant. The SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – American dermatologists are now gaining access to a lot of new hyaluronic acid-based fillers, designed to address limitations in the older, tried-and-true product lines, according to Nowell Solish, MD.
These products have been available in Canada for years. Dr. Solish, a dermatologist at the University of Toronto, shared insights regarding their optimal use, based on his extensive experience with them.
Allergan’s earlier Juvéderm Ultra range of dermal fillers is based on Hylacross, which utilizes crosslinked high–molecular weight HA.
“These products have been around a long time and have lots of benefits, but there were definitely some things missing in the product line,” he explained. “We wanted more control of gel swelling – that is, how much water the hyaluronic acid takes up.”
The Vycross technology employs a proprietary mix of low– and high–molecular weight HA, which results in a highly crosslinked gel that’s moldable immediately after injection, displays minimal gel swelling, and is designed to last longer than earlier-generation fillers.
The main difference between the three products lies in their HA concentrations: Juvéderm Voluma XC has the highest concentration of HA and Juvéderm Volbella XC the lowest, with Volift in between.
The company claims that outcomes with Volbella and Volift last up to 12 months, while Voluma outcomes lasts for up to 24 months. Dr. Solish suggested that his American colleagues take that with a grain of salt.
“I would say I always underpromise and overdeliver with my patients,” he noted. “I think you can probably detect Voluma at 2 years, but, the question is, how good is the effect? How happy is the patient? I think 2 years is a little bit of a stretch. I think it lasts for about 9 months to a year before reinjection.”
Voluma has been available in the United States for several years, while Dr. Solish has been using it far longer. His impression is that Voluma is great for creating volume, especially in the cheeks, midface, and submalar area. He finds that he gets his best results by implanting the product in a series of small, 0.2-mL, tent-like boluses. The reinjection volume is typically substantially less than that employed in initial treatment.
Volbella received approval from the FDA in autumn 2016 for perioral injection and is just now reaching the U.S. marketplace.
“In my humble opinion, I don’t think Volbella is really good for volume,” he explained. “I think it’s great for what I call lip hydration, to give that lip a lipstick look. Where I find that I use this product the most is for the perioral rhytids – the vertical lip lines people sometimes call smokers’ lines. I implant it in the lip mucosa to straighten out the folds.”
Dr. Solish cautioned that Volbella is a fast-flowing product.
“The thing you have to be careful about with Volbella is it has a very low extrusion force,” he noted. “That means it’s very easy to unload the syringe and get too much product out. And there’s no question that there’s a direct correlation between speed of injection and adverse events, mainly edema. So, just remember to slow your hand down, or off-label to add a 31- or even 32-gauge needle to the syringe.”
Volift is not yet approved in the United States, but it’s coming. Dr. Solish called it “a good workhorse product” for mild-to-moderate lines around the face.
“Sales will be much higher than for Volbella, because Volift is great for the in-between things,” the dermatologist continued. “You have Voluma for volume on the midface and cheeks, but Volift is great for nasolabial folds and, especially, for marionette lines and smile lines, where you don’t want a lot of bulk.”
The main adverse event encountered with any of the three products is delayed-onset development of nonpainful inflammatory nodules arising 3-6 months post injection. In one Canadian study, the incidence was less than 0.5% (Dermatol Surg. 2015 Sep;41[9]:1060-7).
Dr. Solish recommended treating the nodules with weekly or biweekly intralesional injections of hyaluronidase, followed by intralesional injections of 0.1 mL/cm2 of triamcinolone (Kenalog) at 2.5 mg/mL to 5.0 mg/mL.
Turning to Galderma’s NASHA technology, Dr. Solish explained that it relies on naturally occurring entanglement of HA chains to create gel particles formulated at 20 mg/dL. By varying the gel particle size and the amount of crosslinking, the company has created a series of products with different properties.
Restylane Refyne features smaller-size particles and less crosslinking, which makes for a softer gel. It’s an excellent option for marionette lines, mild nasolabial folds, and small perioral lines, and “it’s my absolute go-to for tear troughs,” Dr. Solish said.
In contrast, Restylane Defyne has bigger gel particles and more extensive HA crosslinking. It is firmer than Refyne and is best suited for achieving lift and volume. He implants it in the cheeks, forehead, temples, and deeper nasolabial folds.
In addition to these two products, which are new to the United States, Galderma has rebranded Perlane as Restylane Lyft, approved for midfacial augmentation. Another product, Restylane Silk, is similar to Volbella in that it is fast-flowing and not a big volumizer. Dr. Solish called it “lipstick in a syringe,” best suited for improving definition of the lips and for addressing perioral fine lines.
Dr. Solish reported serving as an investigator and/or consultant for Allergan, Galderma, Indeed, Merz, Revance Therapeutics, and Valeant. The SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
New topical field therapies on the way for actinic keratoses
WAILEA, HAWAII – The search is on for new topical therapies for actinic keratoses (AKs) that patients will find more appealing than what’s now available, according to Neal Bhatia, MD.
Compliance with current topical field agents for actinic keratoses is not great. Many patients balk at the intense local skin reactions these agents elicit. There is a misplaced sense, especially among patients who don’t grasp the relationship between AKs and squamous cell carcinoma, that the treatment is worse than the disease, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
One that he said he is particularly excited about is a novel formulation of 4% 5-fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil. In a recently published, double-blind, multicenter clinical trial involving 841 patients, once-daily application of this product for 4 weeks provided better outcomes and superior tolerability, compared with the old-school regimen of 5% 5-FU cream twice daily.
One hundred percent of patients on 4% 5-FU in peanut oil achieved at least 75% clearance of AKs, as did 95% of those on twice daily 5% 5-FU. The incidence of application site skin irritation in the group on the novel product was only 30%, compared with 60% in the comparison group (J Drugs Dermatol. 2016 Oct 1;15[10]:1218-24).
The peanut oil provided a moisturizing effect and was safe even in patients with peanut allergy, Dr. Bhatia noted.
Another product in development as a topical field therapy for AKs is ingenol disoxate gel, a relative of ingenol mebutate (Picato). Unlike ingenol mebutate, ingenol disoxate remains stable without refrigeration. It’s also a more potent activator of protein kinase C. In mouse models, it shows significantly more cytotoxic potency than does ingenol mebutate.
Based upon the favorable results of a short-term, double-blind phase II study, Leo Pharma now has ingenol disoxate in larger clinical trials as field therapy for AKs on the full face, scalp, or chest, with treatment of larger surface areas than those for which ingenol mebutate is approved (J Dermatolog Treat. 2017 Apr 4:1-7).
Actikerall is also in the developmental pipeline. It consists of 0.5% 5-FU, in combination with 10% salicylic acid, in a film-forming base. Developed by Almirall, it is marketed in Canada by Cipher Pharmaceuticals.
SR-T100 gel utilizes as its active ingredient an antiproliferative extract of Solanum lycocarpum, the Brazilian wolf apple. Taiwan-based G & E Herbal Biotechnology is developing the product, which is in an ongoing phase II clinical trial.
Other novel agents for topical field therapy in phase II studies are KX2-391 ointment, a dual Src kinase/tubulin polymerization inhibitor that causes apoptosis of hyperproliferating cells, under development by Athenex, and Vidac Pharma’s VDA-1102 ointment, which selectively triggers apoptosis in neoplastic cells by modulating voltage-dependent anion channel 1/hexokinase enzyme 2, with minimal impact upon surrounding normal cells.
The principle underlying topical field therapy, compared with simply freezing AKs once they arise, is straightforward, Dr. Bhatia stressed. “It’s the difference between treating only what we can see and treating what’s also on the way.”
Dr. Bhatia reported having financial relationships with more than two dozen pharmaceutical companies. SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – The search is on for new topical therapies for actinic keratoses (AKs) that patients will find more appealing than what’s now available, according to Neal Bhatia, MD.
Compliance with current topical field agents for actinic keratoses is not great. Many patients balk at the intense local skin reactions these agents elicit. There is a misplaced sense, especially among patients who don’t grasp the relationship between AKs and squamous cell carcinoma, that the treatment is worse than the disease, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
One that he said he is particularly excited about is a novel formulation of 4% 5-fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil. In a recently published, double-blind, multicenter clinical trial involving 841 patients, once-daily application of this product for 4 weeks provided better outcomes and superior tolerability, compared with the old-school regimen of 5% 5-FU cream twice daily.
One hundred percent of patients on 4% 5-FU in peanut oil achieved at least 75% clearance of AKs, as did 95% of those on twice daily 5% 5-FU. The incidence of application site skin irritation in the group on the novel product was only 30%, compared with 60% in the comparison group (J Drugs Dermatol. 2016 Oct 1;15[10]:1218-24).
The peanut oil provided a moisturizing effect and was safe even in patients with peanut allergy, Dr. Bhatia noted.
Another product in development as a topical field therapy for AKs is ingenol disoxate gel, a relative of ingenol mebutate (Picato). Unlike ingenol mebutate, ingenol disoxate remains stable without refrigeration. It’s also a more potent activator of protein kinase C. In mouse models, it shows significantly more cytotoxic potency than does ingenol mebutate.
Based upon the favorable results of a short-term, double-blind phase II study, Leo Pharma now has ingenol disoxate in larger clinical trials as field therapy for AKs on the full face, scalp, or chest, with treatment of larger surface areas than those for which ingenol mebutate is approved (J Dermatolog Treat. 2017 Apr 4:1-7).
Actikerall is also in the developmental pipeline. It consists of 0.5% 5-FU, in combination with 10% salicylic acid, in a film-forming base. Developed by Almirall, it is marketed in Canada by Cipher Pharmaceuticals.
SR-T100 gel utilizes as its active ingredient an antiproliferative extract of Solanum lycocarpum, the Brazilian wolf apple. Taiwan-based G & E Herbal Biotechnology is developing the product, which is in an ongoing phase II clinical trial.
Other novel agents for topical field therapy in phase II studies are KX2-391 ointment, a dual Src kinase/tubulin polymerization inhibitor that causes apoptosis of hyperproliferating cells, under development by Athenex, and Vidac Pharma’s VDA-1102 ointment, which selectively triggers apoptosis in neoplastic cells by modulating voltage-dependent anion channel 1/hexokinase enzyme 2, with minimal impact upon surrounding normal cells.
The principle underlying topical field therapy, compared with simply freezing AKs once they arise, is straightforward, Dr. Bhatia stressed. “It’s the difference between treating only what we can see and treating what’s also on the way.”
Dr. Bhatia reported having financial relationships with more than two dozen pharmaceutical companies. SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – The search is on for new topical therapies for actinic keratoses (AKs) that patients will find more appealing than what’s now available, according to Neal Bhatia, MD.
Compliance with current topical field agents for actinic keratoses is not great. Many patients balk at the intense local skin reactions these agents elicit. There is a misplaced sense, especially among patients who don’t grasp the relationship between AKs and squamous cell carcinoma, that the treatment is worse than the disease, Dr. Bhatia said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
One that he said he is particularly excited about is a novel formulation of 4% 5-fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil. In a recently published, double-blind, multicenter clinical trial involving 841 patients, once-daily application of this product for 4 weeks provided better outcomes and superior tolerability, compared with the old-school regimen of 5% 5-FU cream twice daily.
One hundred percent of patients on 4% 5-FU in peanut oil achieved at least 75% clearance of AKs, as did 95% of those on twice daily 5% 5-FU. The incidence of application site skin irritation in the group on the novel product was only 30%, compared with 60% in the comparison group (J Drugs Dermatol. 2016 Oct 1;15[10]:1218-24).
The peanut oil provided a moisturizing effect and was safe even in patients with peanut allergy, Dr. Bhatia noted.
Another product in development as a topical field therapy for AKs is ingenol disoxate gel, a relative of ingenol mebutate (Picato). Unlike ingenol mebutate, ingenol disoxate remains stable without refrigeration. It’s also a more potent activator of protein kinase C. In mouse models, it shows significantly more cytotoxic potency than does ingenol mebutate.
Based upon the favorable results of a short-term, double-blind phase II study, Leo Pharma now has ingenol disoxate in larger clinical trials as field therapy for AKs on the full face, scalp, or chest, with treatment of larger surface areas than those for which ingenol mebutate is approved (J Dermatolog Treat. 2017 Apr 4:1-7).
Actikerall is also in the developmental pipeline. It consists of 0.5% 5-FU, in combination with 10% salicylic acid, in a film-forming base. Developed by Almirall, it is marketed in Canada by Cipher Pharmaceuticals.
SR-T100 gel utilizes as its active ingredient an antiproliferative extract of Solanum lycocarpum, the Brazilian wolf apple. Taiwan-based G & E Herbal Biotechnology is developing the product, which is in an ongoing phase II clinical trial.
Other novel agents for topical field therapy in phase II studies are KX2-391 ointment, a dual Src kinase/tubulin polymerization inhibitor that causes apoptosis of hyperproliferating cells, under development by Athenex, and Vidac Pharma’s VDA-1102 ointment, which selectively triggers apoptosis in neoplastic cells by modulating voltage-dependent anion channel 1/hexokinase enzyme 2, with minimal impact upon surrounding normal cells.
The principle underlying topical field therapy, compared with simply freezing AKs once they arise, is straightforward, Dr. Bhatia stressed. “It’s the difference between treating only what we can see and treating what’s also on the way.”
Dr. Bhatia reported having financial relationships with more than two dozen pharmaceutical companies. SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
What’s old is new in topical psoriasis therapy
WAILEA, HAWAII – A fixed combination of halobetasol and tazarotene formulated as a once-daily lotion proved safe and effective for patients with moderate or severe plaque psoriasis in a phase II randomized clinical trial, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The rationale for developing this product is that it should provide the efficacy of a class 1 superpotent topical corticosteroid, albeit with the topical retinoid lessening concern about the possibility of steroid-induced skin atrophy and other long-term safety issues, explained Dr. Stein Gold, director of dermatology research at Henry Ford Health System in Detroit.
The double-blind, multicenter, 8-week, phase II study included 212 patients randomized 2:2:1 to once-daily application of fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% lotion, either topical agent as monotherapy, or vehicle. Ninety percent of participants had moderate plaque psoriasis as defined by a baseline Investigator’s Global Assessment (IGA) score of 3 and a median 5% body surface area involvement. The remaining patients were classified as having severe psoriasis, with a baseline IGA of 4, but no one with psoriasis over more than 12% of their body surface area was eligible for the trial.
The fixed-combination lotion, known for now as IDP-118, established superior efficacy over placebo by 2 weeks. At week 8, treatment success, as defined by at least a two-grade improvement from baseline in IGA score plus a rating of clear or almost clear, was documented in 53% of the IDP-118 lotion group, compared with 33% on halobetasol propionate monotherapy, 19% with tazarotene alone, and 10% with vehicle, Dr. Stein Gold reported.
Each patient had a target lesion 25-32 cm2 in size, which was designated for careful assessment of changes in the domains of lesional erythema, plaque elevation, and scaling. At week 8, the IDP-118 had a target lesion treatment success rate of 54% for erythema, 68% for plaque elevation, and 64% for scaling, she said.
The treatment discontinuation rate was 3.4% in the IDP-118 group, 12.1% with tazarotene, zero for halobetasol propionate, and 3.2% for vehicle. The most frequently reported treatment-emergent adverse events were mild or moderate application-site reactions. Skin atrophy was rare. No treatment-related serious adverse events occurred.
A 555-patient, phase III, open-label, 12-month safety study of IDP-118 is due to be completed later in 2017.
The phase II study was funded by Valeant Pharmaceuticals. Dr. Stein Gold reported serving as an investigator, advisor, and speaker for the company. SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – A fixed combination of halobetasol and tazarotene formulated as a once-daily lotion proved safe and effective for patients with moderate or severe plaque psoriasis in a phase II randomized clinical trial, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The rationale for developing this product is that it should provide the efficacy of a class 1 superpotent topical corticosteroid, albeit with the topical retinoid lessening concern about the possibility of steroid-induced skin atrophy and other long-term safety issues, explained Dr. Stein Gold, director of dermatology research at Henry Ford Health System in Detroit.
The double-blind, multicenter, 8-week, phase II study included 212 patients randomized 2:2:1 to once-daily application of fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% lotion, either topical agent as monotherapy, or vehicle. Ninety percent of participants had moderate plaque psoriasis as defined by a baseline Investigator’s Global Assessment (IGA) score of 3 and a median 5% body surface area involvement. The remaining patients were classified as having severe psoriasis, with a baseline IGA of 4, but no one with psoriasis over more than 12% of their body surface area was eligible for the trial.
The fixed-combination lotion, known for now as IDP-118, established superior efficacy over placebo by 2 weeks. At week 8, treatment success, as defined by at least a two-grade improvement from baseline in IGA score plus a rating of clear or almost clear, was documented in 53% of the IDP-118 lotion group, compared with 33% on halobetasol propionate monotherapy, 19% with tazarotene alone, and 10% with vehicle, Dr. Stein Gold reported.
Each patient had a target lesion 25-32 cm2 in size, which was designated for careful assessment of changes in the domains of lesional erythema, plaque elevation, and scaling. At week 8, the IDP-118 had a target lesion treatment success rate of 54% for erythema, 68% for plaque elevation, and 64% for scaling, she said.
The treatment discontinuation rate was 3.4% in the IDP-118 group, 12.1% with tazarotene, zero for halobetasol propionate, and 3.2% for vehicle. The most frequently reported treatment-emergent adverse events were mild or moderate application-site reactions. Skin atrophy was rare. No treatment-related serious adverse events occurred.
A 555-patient, phase III, open-label, 12-month safety study of IDP-118 is due to be completed later in 2017.
The phase II study was funded by Valeant Pharmaceuticals. Dr. Stein Gold reported serving as an investigator, advisor, and speaker for the company. SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – A fixed combination of halobetasol and tazarotene formulated as a once-daily lotion proved safe and effective for patients with moderate or severe plaque psoriasis in a phase II randomized clinical trial, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The rationale for developing this product is that it should provide the efficacy of a class 1 superpotent topical corticosteroid, albeit with the topical retinoid lessening concern about the possibility of steroid-induced skin atrophy and other long-term safety issues, explained Dr. Stein Gold, director of dermatology research at Henry Ford Health System in Detroit.
The double-blind, multicenter, 8-week, phase II study included 212 patients randomized 2:2:1 to once-daily application of fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% lotion, either topical agent as monotherapy, or vehicle. Ninety percent of participants had moderate plaque psoriasis as defined by a baseline Investigator’s Global Assessment (IGA) score of 3 and a median 5% body surface area involvement. The remaining patients were classified as having severe psoriasis, with a baseline IGA of 4, but no one with psoriasis over more than 12% of their body surface area was eligible for the trial.
The fixed-combination lotion, known for now as IDP-118, established superior efficacy over placebo by 2 weeks. At week 8, treatment success, as defined by at least a two-grade improvement from baseline in IGA score plus a rating of clear or almost clear, was documented in 53% of the IDP-118 lotion group, compared with 33% on halobetasol propionate monotherapy, 19% with tazarotene alone, and 10% with vehicle, Dr. Stein Gold reported.
Each patient had a target lesion 25-32 cm2 in size, which was designated for careful assessment of changes in the domains of lesional erythema, plaque elevation, and scaling. At week 8, the IDP-118 had a target lesion treatment success rate of 54% for erythema, 68% for plaque elevation, and 64% for scaling, she said.
The treatment discontinuation rate was 3.4% in the IDP-118 group, 12.1% with tazarotene, zero for halobetasol propionate, and 3.2% for vehicle. The most frequently reported treatment-emergent adverse events were mild or moderate application-site reactions. Skin atrophy was rare. No treatment-related serious adverse events occurred.
A 555-patient, phase III, open-label, 12-month safety study of IDP-118 is due to be completed later in 2017.
The phase II study was funded by Valeant Pharmaceuticals. Dr. Stein Gold reported serving as an investigator, advisor, and speaker for the company. SDEF and this news organization are owned by the same parent company.
Key clinical point:
Major finding: An investigational fixed-combination lotion consisting of halobetasol propionate 0.01% and tazarotene 0.045% achieved scores of clear or almost clear in 53% of patients, significantly better than either component as monotherapy.
Data source: This phase II, double-blind, multicenter, vehicle-controlled, 8-week randomized clinical trial included 212 patients with moderate or severe plaque psoriasis.
Disclosures: The study was funded by Valeant Pharmaceuticals. The presenter reported serving as an investigator, advisor, and speaker for the company.
Clinicians still seek the best uses for apremilast
WAILEA, HAWAII – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.
“You have a drug that’s modest with regard to clearing psoriasis and it’s modest in controlling psoriatic arthritis. So you have to ask yourself what’s the patient population for this drug. I would just say that in my hands – and this is off-label – I use it only in patients with mild to moderate psoriasis,” Dr. Leonardi said.
“We all have psoriasis patients who come in with 3% or 4% of their skin involved, they’re actually using the class I topical steroids that I prescribe for them, yet they’re still not clear or almost clear and they want more. At that point, that’s when I might take them down this pathway and put them on apremilast along with a topical steroid. And I think that’s the appropriate place for this drug. I don’t use it in patients with 10% or more body surface area involvement,” he said.
He added that he would like to be able to prescribe apremilast in conjunction with a biologic agent in patients with more severe psoriasis to obtain synergistic efficacy, but payers balk at that because, at close to $3,000 per month, apremilast costs far more than methotrexate and other generic conventional disease-modifying antirheumatic drugs.
“The insurance industry is all over this drug. They require preauthorization, and they tell me, ‘No way, have a nice day,’ ” according to the dermatologist.
Dr. Leonardi described a couple of other practical caveats regarding apremilast. In patients with an estimated glomerular filtration rate below 30 mL/min per 1.73 m2, a dose reduction to 30 mg once daily in the morning is necessary. And apremilast is not recommended for use in patients who are on a strong inducer of the CYP 450 enzyme, such as rifampin or phenytoin.
An intriguing side effect of apremilast is that it causes weight loss: A 5%-10% weight loss was seen in the major psoriasis clinical trials. But it’s been established that there is no correlation at all between the weight loss and clinical efficacy for skin clearance.
What efficacy can be anticipated?
In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis (J Am Acad Dermatol. 2015 Jul;73[1]:37-49), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.
Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo (Ann Rheum Dis. 2014 Jun;73[6]:1020-6). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.
On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.
Symposium codirector Linda Stein Gold, MD, director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.
Finding potential in off-label use
“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.
Dr. Leonardi remained unpersuaded.
“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”
Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.
SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.
“You have a drug that’s modest with regard to clearing psoriasis and it’s modest in controlling psoriatic arthritis. So you have to ask yourself what’s the patient population for this drug. I would just say that in my hands – and this is off-label – I use it only in patients with mild to moderate psoriasis,” Dr. Leonardi said.
“We all have psoriasis patients who come in with 3% or 4% of their skin involved, they’re actually using the class I topical steroids that I prescribe for them, yet they’re still not clear or almost clear and they want more. At that point, that’s when I might take them down this pathway and put them on apremilast along with a topical steroid. And I think that’s the appropriate place for this drug. I don’t use it in patients with 10% or more body surface area involvement,” he said.
He added that he would like to be able to prescribe apremilast in conjunction with a biologic agent in patients with more severe psoriasis to obtain synergistic efficacy, but payers balk at that because, at close to $3,000 per month, apremilast costs far more than methotrexate and other generic conventional disease-modifying antirheumatic drugs.
“The insurance industry is all over this drug. They require preauthorization, and they tell me, ‘No way, have a nice day,’ ” according to the dermatologist.
Dr. Leonardi described a couple of other practical caveats regarding apremilast. In patients with an estimated glomerular filtration rate below 30 mL/min per 1.73 m2, a dose reduction to 30 mg once daily in the morning is necessary. And apremilast is not recommended for use in patients who are on a strong inducer of the CYP 450 enzyme, such as rifampin or phenytoin.
An intriguing side effect of apremilast is that it causes weight loss: A 5%-10% weight loss was seen in the major psoriasis clinical trials. But it’s been established that there is no correlation at all between the weight loss and clinical efficacy for skin clearance.
What efficacy can be anticipated?
In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis (J Am Acad Dermatol. 2015 Jul;73[1]:37-49), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.
Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo (Ann Rheum Dis. 2014 Jun;73[6]:1020-6). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.
On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.
Symposium codirector Linda Stein Gold, MD, director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.
Finding potential in off-label use
“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.
Dr. Leonardi remained unpersuaded.
“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”
Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.
SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.
“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.
“You have a drug that’s modest with regard to clearing psoriasis and it’s modest in controlling psoriatic arthritis. So you have to ask yourself what’s the patient population for this drug. I would just say that in my hands – and this is off-label – I use it only in patients with mild to moderate psoriasis,” Dr. Leonardi said.
“We all have psoriasis patients who come in with 3% or 4% of their skin involved, they’re actually using the class I topical steroids that I prescribe for them, yet they’re still not clear or almost clear and they want more. At that point, that’s when I might take them down this pathway and put them on apremilast along with a topical steroid. And I think that’s the appropriate place for this drug. I don’t use it in patients with 10% or more body surface area involvement,” he said.
He added that he would like to be able to prescribe apremilast in conjunction with a biologic agent in patients with more severe psoriasis to obtain synergistic efficacy, but payers balk at that because, at close to $3,000 per month, apremilast costs far more than methotrexate and other generic conventional disease-modifying antirheumatic drugs.
“The insurance industry is all over this drug. They require preauthorization, and they tell me, ‘No way, have a nice day,’ ” according to the dermatologist.
Dr. Leonardi described a couple of other practical caveats regarding apremilast. In patients with an estimated glomerular filtration rate below 30 mL/min per 1.73 m2, a dose reduction to 30 mg once daily in the morning is necessary. And apremilast is not recommended for use in patients who are on a strong inducer of the CYP 450 enzyme, such as rifampin or phenytoin.
An intriguing side effect of apremilast is that it causes weight loss: A 5%-10% weight loss was seen in the major psoriasis clinical trials. But it’s been established that there is no correlation at all between the weight loss and clinical efficacy for skin clearance.
What efficacy can be anticipated?
In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis (J Am Acad Dermatol. 2015 Jul;73[1]:37-49), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.
Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo (Ann Rheum Dis. 2014 Jun;73[6]:1020-6). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.
On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.
Symposium codirector Linda Stein Gold, MD, director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.
Finding potential in off-label use
“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.
Dr. Leonardi remained unpersuaded.
“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”
Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.
SDEF and this news organization are owned by the same parent company.
How will crisaborole for atopic dermatitis fit into clinical practice?
WAILEA, HAWAII – With the recent approval of crisaborole ointment 2% for the treatment of atopic dermatitis, the question of how to best utilize this novel drug in daily clinical practice was put to two atopic dermatitis experts at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Research Foundation.
Two of these experts, Lawrence F. Eichenfield, MD, and Wynnis L. Tom, MD, have garnered extensive clinical trials experience with crisaborole (Eucrisa), which, in December 2016, became the first prescription drug approved by the Food and Drug Administration for atopic dermatitis (AD) in more than 10 years. The topical phosphodiesterase-4 inhibitor is indicated for twice-daily treatment of patients aged 2 years and older with mild to moderate AD.
“Topical steroids are the most cost-effective medicine for the management of acute flares of atopic dermatitis. And if I can then take patients down to only intermittent use of topical corticosteroids of mid-strength or lower, depending on patient age, I’ll probably hang in and do just that,” said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego.
“But, when I have patients with more persistent disease, frequent flaring where I can’t get by with just twice-a-week topical steroids, or ... sensitive areas where I need to avoid steroid atrophy, that’s when I’m likely to incorporate a nonsteroidal agent into regimens of care. Traditionally, over the past 15-18 years, that’s been either with topical tacrolimus [Protopic] or pimecrolimus [Elidel]. And now crisaborole will fit right in there,” he continued.
As for how long to keep patients on crisaborole, Dr. Eichenfield noted that the package labeling “is pretty open.” It doesn’t address the question of treatment duration, and the patient handout that accompanies the tube of ointment simply states, “Use [crisaborole] Eucrisa exactly as your health care provider tells you to use it.”
“In a no-data situation such as this, I’ll probably try to see if use a few times a week or in a mix/match between corticosteroids, a topical calcineurin inhibitor, and crisaborole will provide decent long-term disease control,” Dr. Eichenfield said.
The important, remaining questions regarding crisaborole include, Is it comparatively efficient? – a question that will require head-to-head clinical trials. Is it cost effective? Will it be effective and safe in children younger than 2 years of age? Is it safe beyond 1 year of use? – a particularly important question, given that the phase III clinical trials were only a month long, the dermatologist added.
Dr. Eichenfield emphasized that he was offering only his personal opinion on the use of crisaborole in response to audience questions. Eventually, guidelines committees will formally address how to incorporate the new drug into a sound treatment strategy.
Dr. Tom, like Dr. Eichenfield, was a coauthor of the two pivotal phase III randomized trials of crisaborole, which found infrequent and minimal side effects along with significant improvement of formal quality of life measures (J Am Acad Dermatol. 2016 Sep;75[3]:494-503.e4).
She said that one way she’ll immediately put the new topical agent to work is in treating disease on the face and other sensitive skin areas. The drug’s steroid-sparing ability is also a major asset, given how many parents of children with AD are steroid phobic.
“I’m certainly not going to give up on topical steroids, but anything that enables me to lessen their use is a comfort for parents. That’s really important,” observed Dr. Tom of the University of California, San Diego, and Rady Children’s Hospital.
Both pediatric dermatologists reported having received research grants from or serving as consultants to roughly half-a-dozen pharmaceutical companies, including Anacor/Pfizer, which markets crisaborole.
SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – With the recent approval of crisaborole ointment 2% for the treatment of atopic dermatitis, the question of how to best utilize this novel drug in daily clinical practice was put to two atopic dermatitis experts at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Research Foundation.
Two of these experts, Lawrence F. Eichenfield, MD, and Wynnis L. Tom, MD, have garnered extensive clinical trials experience with crisaborole (Eucrisa), which, in December 2016, became the first prescription drug approved by the Food and Drug Administration for atopic dermatitis (AD) in more than 10 years. The topical phosphodiesterase-4 inhibitor is indicated for twice-daily treatment of patients aged 2 years and older with mild to moderate AD.
“Topical steroids are the most cost-effective medicine for the management of acute flares of atopic dermatitis. And if I can then take patients down to only intermittent use of topical corticosteroids of mid-strength or lower, depending on patient age, I’ll probably hang in and do just that,” said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego.
“But, when I have patients with more persistent disease, frequent flaring where I can’t get by with just twice-a-week topical steroids, or ... sensitive areas where I need to avoid steroid atrophy, that’s when I’m likely to incorporate a nonsteroidal agent into regimens of care. Traditionally, over the past 15-18 years, that’s been either with topical tacrolimus [Protopic] or pimecrolimus [Elidel]. And now crisaborole will fit right in there,” he continued.
As for how long to keep patients on crisaborole, Dr. Eichenfield noted that the package labeling “is pretty open.” It doesn’t address the question of treatment duration, and the patient handout that accompanies the tube of ointment simply states, “Use [crisaborole] Eucrisa exactly as your health care provider tells you to use it.”
“In a no-data situation such as this, I’ll probably try to see if use a few times a week or in a mix/match between corticosteroids, a topical calcineurin inhibitor, and crisaborole will provide decent long-term disease control,” Dr. Eichenfield said.
The important, remaining questions regarding crisaborole include, Is it comparatively efficient? – a question that will require head-to-head clinical trials. Is it cost effective? Will it be effective and safe in children younger than 2 years of age? Is it safe beyond 1 year of use? – a particularly important question, given that the phase III clinical trials were only a month long, the dermatologist added.
Dr. Eichenfield emphasized that he was offering only his personal opinion on the use of crisaborole in response to audience questions. Eventually, guidelines committees will formally address how to incorporate the new drug into a sound treatment strategy.
Dr. Tom, like Dr. Eichenfield, was a coauthor of the two pivotal phase III randomized trials of crisaborole, which found infrequent and minimal side effects along with significant improvement of formal quality of life measures (J Am Acad Dermatol. 2016 Sep;75[3]:494-503.e4).
She said that one way she’ll immediately put the new topical agent to work is in treating disease on the face and other sensitive skin areas. The drug’s steroid-sparing ability is also a major asset, given how many parents of children with AD are steroid phobic.
“I’m certainly not going to give up on topical steroids, but anything that enables me to lessen their use is a comfort for parents. That’s really important,” observed Dr. Tom of the University of California, San Diego, and Rady Children’s Hospital.
Both pediatric dermatologists reported having received research grants from or serving as consultants to roughly half-a-dozen pharmaceutical companies, including Anacor/Pfizer, which markets crisaborole.
SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – With the recent approval of crisaborole ointment 2% for the treatment of atopic dermatitis, the question of how to best utilize this novel drug in daily clinical practice was put to two atopic dermatitis experts at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Research Foundation.
Two of these experts, Lawrence F. Eichenfield, MD, and Wynnis L. Tom, MD, have garnered extensive clinical trials experience with crisaborole (Eucrisa), which, in December 2016, became the first prescription drug approved by the Food and Drug Administration for atopic dermatitis (AD) in more than 10 years. The topical phosphodiesterase-4 inhibitor is indicated for twice-daily treatment of patients aged 2 years and older with mild to moderate AD.
“Topical steroids are the most cost-effective medicine for the management of acute flares of atopic dermatitis. And if I can then take patients down to only intermittent use of topical corticosteroids of mid-strength or lower, depending on patient age, I’ll probably hang in and do just that,” said Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego.
“But, when I have patients with more persistent disease, frequent flaring where I can’t get by with just twice-a-week topical steroids, or ... sensitive areas where I need to avoid steroid atrophy, that’s when I’m likely to incorporate a nonsteroidal agent into regimens of care. Traditionally, over the past 15-18 years, that’s been either with topical tacrolimus [Protopic] or pimecrolimus [Elidel]. And now crisaborole will fit right in there,” he continued.
As for how long to keep patients on crisaborole, Dr. Eichenfield noted that the package labeling “is pretty open.” It doesn’t address the question of treatment duration, and the patient handout that accompanies the tube of ointment simply states, “Use [crisaborole] Eucrisa exactly as your health care provider tells you to use it.”
“In a no-data situation such as this, I’ll probably try to see if use a few times a week or in a mix/match between corticosteroids, a topical calcineurin inhibitor, and crisaborole will provide decent long-term disease control,” Dr. Eichenfield said.
The important, remaining questions regarding crisaborole include, Is it comparatively efficient? – a question that will require head-to-head clinical trials. Is it cost effective? Will it be effective and safe in children younger than 2 years of age? Is it safe beyond 1 year of use? – a particularly important question, given that the phase III clinical trials were only a month long, the dermatologist added.
Dr. Eichenfield emphasized that he was offering only his personal opinion on the use of crisaborole in response to audience questions. Eventually, guidelines committees will formally address how to incorporate the new drug into a sound treatment strategy.
Dr. Tom, like Dr. Eichenfield, was a coauthor of the two pivotal phase III randomized trials of crisaborole, which found infrequent and minimal side effects along with significant improvement of formal quality of life measures (J Am Acad Dermatol. 2016 Sep;75[3]:494-503.e4).
She said that one way she’ll immediately put the new topical agent to work is in treating disease on the face and other sensitive skin areas. The drug’s steroid-sparing ability is also a major asset, given how many parents of children with AD are steroid phobic.
“I’m certainly not going to give up on topical steroids, but anything that enables me to lessen their use is a comfort for parents. That’s really important,” observed Dr. Tom of the University of California, San Diego, and Rady Children’s Hospital.
Both pediatric dermatologists reported having received research grants from or serving as consultants to roughly half-a-dozen pharmaceutical companies, including Anacor/Pfizer, which markets crisaborole.
SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
Monthly lab testing for isotretinoin? No need, expert says
WAILEA, HAWAII – Many physicians perform laboratory monitoring monthly when prescribing isotretinoin for severe acne, but recent evidence indicates that’s excessive, according to Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society.
She pointed to a meta-analysis of isotretinoin studies, which she called “a game changer” in her own dermatology practice in Birmingham, Ala.
The investigators published a meta-analysis of 26 studies including 1,574 isotretinoin-treated acne patients with serial laboratory values available (JAMA Dermatol. 2016 Jan;152[1]:35-44). They were particularly interested in patterns of elevation in triglycerides because that’s the most common lab abnormality associated with the use of isotretinoin. Indeed, the package insert states that, in the original clinical trials, one in four isotretinoin-treated patients developed high triglycerides.
The meta-analysis demonstrated that triglyceride levels rose by a mean of 45.3 mg/dL after 8 weeks on isotretinoin. Notably, however, the mean difference in triglycerides between baseline and 20 weeks was essentially the same at 45.6 mg/dL.
“Therefore, if you’re going to have a change in triglycerides, you’re going to have it early. If it’s good at week 8, it should be good at week 20. And if it’s not good at week 8, you probably ought to keep checking,” Dr. Harper said.
Similarly, there was no substantial late effect of isotretinoin on total cholesterol.
The investigators determined that they had insufficient data to draw conclusions regarding late changes in liver function tests. For guidance on that score, Dr. Harper turned to an earlier study of nearly 14,000 isotretinoin-treated patients led by Lee T. Zane, MD, a dermatologist at University of California, San Francisco, and medical director at Anacor.
Dr. Zane and his coinvestigators found that 1.5% of patients experienced a moderate elevation in transaminase levels, and no one experienced high-risk or grade 2 elevations in transaminases, triglycerides, or total cholesterol. Dr. Zane and his coinvestigators also concluded that monitoring white blood cells, platelets, and hemoglobin was meritless (Arch Dermatol. 2006 Aug;142[8]:1016-22).
“I’m not checking white blood cells, platelets, or hemoglobin. I check only triglycerides, total cholesterol, and hepatic function – and a pregnancy test, of course,” Dr. Harper said.
“I’ve practiced for 17 years,” she continued. “I’ve given a lot of people isotretinoin. And I would agree with Lee Zane – we don’t see elevated liver function tests very often with this drug, and when we do there’s often another explanation for why they’re high.”
In her own practice, when a patient on isotretinoin develops a high triglyceride approaching 300 mg/dL, the first thing she does is recheck it and make sure the patient is fasting. If it’s a true elevation, she pulls the dose back because this is a dose-related side effect. She also recommends that the patient begin taking fish oil supplements at a starting dose of 2 g/day. In a handful of refractory patients, she prescribes fenofibrate.
The exceptions she makes to her policy of no further lab testing if the first 2 months are problem free are patients with polycystic ovary syndrome, central obesity, or outright metabolic syndrome, since they are probably already at increased risk for developing lab abnormalities.
Dr. Harper said her acne patients are pleased with her change in practice regarding laboratory monitoring. Coming in for monthly blood work is inconvenient. And some patients really, really do not want to be stuck with a needle.
“We’re saving money, too,” she noted.
Dr. Harper wasn’t the only dermatologist who found the recent meta-analysis persuasive. The report was accompanied by an editorial by physicians uninvolved in the study entitled, “Isotretinoin Laboratory Test Monitoring – A Call to Decrease Testing in an Era of High-Value, Cost-Conscious Care” (JAMA Dermatol. 2016 Jan;152[1]:17-9).
She reported serving on speakers’ bureaus for Allergan, Bayer, Galderma, LaRoche-Posay, Promius, and Valeant.
SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – Many physicians perform laboratory monitoring monthly when prescribing isotretinoin for severe acne, but recent evidence indicates that’s excessive, according to Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society.
She pointed to a meta-analysis of isotretinoin studies, which she called “a game changer” in her own dermatology practice in Birmingham, Ala.
The investigators published a meta-analysis of 26 studies including 1,574 isotretinoin-treated acne patients with serial laboratory values available (JAMA Dermatol. 2016 Jan;152[1]:35-44). They were particularly interested in patterns of elevation in triglycerides because that’s the most common lab abnormality associated with the use of isotretinoin. Indeed, the package insert states that, in the original clinical trials, one in four isotretinoin-treated patients developed high triglycerides.
The meta-analysis demonstrated that triglyceride levels rose by a mean of 45.3 mg/dL after 8 weeks on isotretinoin. Notably, however, the mean difference in triglycerides between baseline and 20 weeks was essentially the same at 45.6 mg/dL.
“Therefore, if you’re going to have a change in triglycerides, you’re going to have it early. If it’s good at week 8, it should be good at week 20. And if it’s not good at week 8, you probably ought to keep checking,” Dr. Harper said.
Similarly, there was no substantial late effect of isotretinoin on total cholesterol.
The investigators determined that they had insufficient data to draw conclusions regarding late changes in liver function tests. For guidance on that score, Dr. Harper turned to an earlier study of nearly 14,000 isotretinoin-treated patients led by Lee T. Zane, MD, a dermatologist at University of California, San Francisco, and medical director at Anacor.
Dr. Zane and his coinvestigators found that 1.5% of patients experienced a moderate elevation in transaminase levels, and no one experienced high-risk or grade 2 elevations in transaminases, triglycerides, or total cholesterol. Dr. Zane and his coinvestigators also concluded that monitoring white blood cells, platelets, and hemoglobin was meritless (Arch Dermatol. 2006 Aug;142[8]:1016-22).
“I’m not checking white blood cells, platelets, or hemoglobin. I check only triglycerides, total cholesterol, and hepatic function – and a pregnancy test, of course,” Dr. Harper said.
“I’ve practiced for 17 years,” she continued. “I’ve given a lot of people isotretinoin. And I would agree with Lee Zane – we don’t see elevated liver function tests very often with this drug, and when we do there’s often another explanation for why they’re high.”
In her own practice, when a patient on isotretinoin develops a high triglyceride approaching 300 mg/dL, the first thing she does is recheck it and make sure the patient is fasting. If it’s a true elevation, she pulls the dose back because this is a dose-related side effect. She also recommends that the patient begin taking fish oil supplements at a starting dose of 2 g/day. In a handful of refractory patients, she prescribes fenofibrate.
The exceptions she makes to her policy of no further lab testing if the first 2 months are problem free are patients with polycystic ovary syndrome, central obesity, or outright metabolic syndrome, since they are probably already at increased risk for developing lab abnormalities.
Dr. Harper said her acne patients are pleased with her change in practice regarding laboratory monitoring. Coming in for monthly blood work is inconvenient. And some patients really, really do not want to be stuck with a needle.
“We’re saving money, too,” she noted.
Dr. Harper wasn’t the only dermatologist who found the recent meta-analysis persuasive. The report was accompanied by an editorial by physicians uninvolved in the study entitled, “Isotretinoin Laboratory Test Monitoring – A Call to Decrease Testing in an Era of High-Value, Cost-Conscious Care” (JAMA Dermatol. 2016 Jan;152[1]:17-9).
She reported serving on speakers’ bureaus for Allergan, Bayer, Galderma, LaRoche-Posay, Promius, and Valeant.
SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – Many physicians perform laboratory monitoring monthly when prescribing isotretinoin for severe acne, but recent evidence indicates that’s excessive, according to Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society.
She pointed to a meta-analysis of isotretinoin studies, which she called “a game changer” in her own dermatology practice in Birmingham, Ala.
The investigators published a meta-analysis of 26 studies including 1,574 isotretinoin-treated acne patients with serial laboratory values available (JAMA Dermatol. 2016 Jan;152[1]:35-44). They were particularly interested in patterns of elevation in triglycerides because that’s the most common lab abnormality associated with the use of isotretinoin. Indeed, the package insert states that, in the original clinical trials, one in four isotretinoin-treated patients developed high triglycerides.
The meta-analysis demonstrated that triglyceride levels rose by a mean of 45.3 mg/dL after 8 weeks on isotretinoin. Notably, however, the mean difference in triglycerides between baseline and 20 weeks was essentially the same at 45.6 mg/dL.
“Therefore, if you’re going to have a change in triglycerides, you’re going to have it early. If it’s good at week 8, it should be good at week 20. And if it’s not good at week 8, you probably ought to keep checking,” Dr. Harper said.
Similarly, there was no substantial late effect of isotretinoin on total cholesterol.
The investigators determined that they had insufficient data to draw conclusions regarding late changes in liver function tests. For guidance on that score, Dr. Harper turned to an earlier study of nearly 14,000 isotretinoin-treated patients led by Lee T. Zane, MD, a dermatologist at University of California, San Francisco, and medical director at Anacor.
Dr. Zane and his coinvestigators found that 1.5% of patients experienced a moderate elevation in transaminase levels, and no one experienced high-risk or grade 2 elevations in transaminases, triglycerides, or total cholesterol. Dr. Zane and his coinvestigators also concluded that monitoring white blood cells, platelets, and hemoglobin was meritless (Arch Dermatol. 2006 Aug;142[8]:1016-22).
“I’m not checking white blood cells, platelets, or hemoglobin. I check only triglycerides, total cholesterol, and hepatic function – and a pregnancy test, of course,” Dr. Harper said.
“I’ve practiced for 17 years,” she continued. “I’ve given a lot of people isotretinoin. And I would agree with Lee Zane – we don’t see elevated liver function tests very often with this drug, and when we do there’s often another explanation for why they’re high.”
In her own practice, when a patient on isotretinoin develops a high triglyceride approaching 300 mg/dL, the first thing she does is recheck it and make sure the patient is fasting. If it’s a true elevation, she pulls the dose back because this is a dose-related side effect. She also recommends that the patient begin taking fish oil supplements at a starting dose of 2 g/day. In a handful of refractory patients, she prescribes fenofibrate.
The exceptions she makes to her policy of no further lab testing if the first 2 months are problem free are patients with polycystic ovary syndrome, central obesity, or outright metabolic syndrome, since they are probably already at increased risk for developing lab abnormalities.
Dr. Harper said her acne patients are pleased with her change in practice regarding laboratory monitoring. Coming in for monthly blood work is inconvenient. And some patients really, really do not want to be stuck with a needle.
“We’re saving money, too,” she noted.
Dr. Harper wasn’t the only dermatologist who found the recent meta-analysis persuasive. The report was accompanied by an editorial by physicians uninvolved in the study entitled, “Isotretinoin Laboratory Test Monitoring – A Call to Decrease Testing in an Era of High-Value, Cost-Conscious Care” (JAMA Dermatol. 2016 Jan;152[1]:17-9).
She reported serving on speakers’ bureaus for Allergan, Bayer, Galderma, LaRoche-Posay, Promius, and Valeant.
SDEF and this news organization are owned by the same parent company.
Redefine dysplastic nevi to stratify cancer risk
WAILEA, HAWAII – It is time for a new system of classifying nevi, according to Ashfaq Marghoob, MD, of Memorial Sloan Kettering Cancer Center, New York.
“It was known for the last 30 or 40 years that we do need to subclassify nevi into groups, so as to better stratify for melanoma risk,” identifying groups of individuals who would benefit most from targeted screening, Dr. Marghoob said in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation. But it has been clear that there are many flaws in the current classification system, he added.
This is beginning to change as new data emerge about gene mutations and other science that can better stratify “or segregate” the nevi into subsets, and “the hope is we will be better able to predict which subsets are associated with melanoma risk either within the lesion itself or poses an increased risk to the patient,” he explained.
“As our understanding grows, we will start to come out with subsets of nevi that have a certain clinical and dermoscopic morphology,” to help predict which patients would benefit most from being monitored very closely, with the aim of detecting – and curing – melanomas early, said Dr. Marghoob, director of Memorial Sloan Kettering’s regional skin cancer clinic in Hauppauge, N.Y.
He had no financial conflicts to disclose.
SDEF and this news organization are owned by the same parent organization.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – It is time for a new system of classifying nevi, according to Ashfaq Marghoob, MD, of Memorial Sloan Kettering Cancer Center, New York.
“It was known for the last 30 or 40 years that we do need to subclassify nevi into groups, so as to better stratify for melanoma risk,” identifying groups of individuals who would benefit most from targeted screening, Dr. Marghoob said in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation. But it has been clear that there are many flaws in the current classification system, he added.
This is beginning to change as new data emerge about gene mutations and other science that can better stratify “or segregate” the nevi into subsets, and “the hope is we will be better able to predict which subsets are associated with melanoma risk either within the lesion itself or poses an increased risk to the patient,” he explained.
“As our understanding grows, we will start to come out with subsets of nevi that have a certain clinical and dermoscopic morphology,” to help predict which patients would benefit most from being monitored very closely, with the aim of detecting – and curing – melanomas early, said Dr. Marghoob, director of Memorial Sloan Kettering’s regional skin cancer clinic in Hauppauge, N.Y.
He had no financial conflicts to disclose.
SDEF and this news organization are owned by the same parent organization.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – It is time for a new system of classifying nevi, according to Ashfaq Marghoob, MD, of Memorial Sloan Kettering Cancer Center, New York.
“It was known for the last 30 or 40 years that we do need to subclassify nevi into groups, so as to better stratify for melanoma risk,” identifying groups of individuals who would benefit most from targeted screening, Dr. Marghoob said in a video interview at the meeting, provided by Global Academy for Medical Education/Skin Disease Education Foundation. But it has been clear that there are many flaws in the current classification system, he added.
This is beginning to change as new data emerge about gene mutations and other science that can better stratify “or segregate” the nevi into subsets, and “the hope is we will be better able to predict which subsets are associated with melanoma risk either within the lesion itself or poses an increased risk to the patient,” he explained.
“As our understanding grows, we will start to come out with subsets of nevi that have a certain clinical and dermoscopic morphology,” to help predict which patients would benefit most from being monitored very closely, with the aim of detecting – and curing – melanomas early, said Dr. Marghoob, director of Memorial Sloan Kettering’s regional skin cancer clinic in Hauppauge, N.Y.
He had no financial conflicts to disclose.
SDEF and this news organization are owned by the same parent organization.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: Advances in noninvasive fat reduction include permanent effects
WAILEA, HAWAII – In the past few years, there have been “exciting” advances in noninvasive techniques to permanently remove fat, according to Suzanne Kilmer, MD, of the department of dermatology, University of California, Davis.
There are devices now available to reduce fat “in a permanent way that’s not injurious, it’s not uncomfortable – patients love it,” Dr. Kilmer said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Currently, the three noninvasive modalities she considers most effective for reducing fat are cryolipolysis, the 1,060-nm laser, and focused pulsed ultrasound. In the interview, she discussed the ways these treatments work and their safety.
With all three, “the fat that goes away stays away,” said Dr. Kilmer, who is director of the Laser and Skin Surgery Center of Northern California, Sacramento. Treatment results in release of fat, which is “cleared like it is as if you ate a cheeseburger,” she added. Interestingly, she said, trials that have looked at whether the fat reduction is accompanied by weight loss have found that, in most cases, the patient’s weight remains stable.
Dr. Kilmer’s disclosures included serving as a consultant and/or researcher for Allergan, Cutera, Cynosure, Cytrellis, Kythera, Lumenis, Merz, Miramar, Sebacia, Sienna Labs, Solta, Zeltiq, and Zift.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – In the past few years, there have been “exciting” advances in noninvasive techniques to permanently remove fat, according to Suzanne Kilmer, MD, of the department of dermatology, University of California, Davis.
There are devices now available to reduce fat “in a permanent way that’s not injurious, it’s not uncomfortable – patients love it,” Dr. Kilmer said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Currently, the three noninvasive modalities she considers most effective for reducing fat are cryolipolysis, the 1,060-nm laser, and focused pulsed ultrasound. In the interview, she discussed the ways these treatments work and their safety.
With all three, “the fat that goes away stays away,” said Dr. Kilmer, who is director of the Laser and Skin Surgery Center of Northern California, Sacramento. Treatment results in release of fat, which is “cleared like it is as if you ate a cheeseburger,” she added. Interestingly, she said, trials that have looked at whether the fat reduction is accompanied by weight loss have found that, in most cases, the patient’s weight remains stable.
Dr. Kilmer’s disclosures included serving as a consultant and/or researcher for Allergan, Cutera, Cynosure, Cytrellis, Kythera, Lumenis, Merz, Miramar, Sebacia, Sienna Labs, Solta, Zeltiq, and Zift.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – In the past few years, there have been “exciting” advances in noninvasive techniques to permanently remove fat, according to Suzanne Kilmer, MD, of the department of dermatology, University of California, Davis.
There are devices now available to reduce fat “in a permanent way that’s not injurious, it’s not uncomfortable – patients love it,” Dr. Kilmer said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Currently, the three noninvasive modalities she considers most effective for reducing fat are cryolipolysis, the 1,060-nm laser, and focused pulsed ultrasound. In the interview, she discussed the ways these treatments work and their safety.
With all three, “the fat that goes away stays away,” said Dr. Kilmer, who is director of the Laser and Skin Surgery Center of Northern California, Sacramento. Treatment results in release of fat, which is “cleared like it is as if you ate a cheeseburger,” she added. Interestingly, she said, trials that have looked at whether the fat reduction is accompanied by weight loss have found that, in most cases, the patient’s weight remains stable.
Dr. Kilmer’s disclosures included serving as a consultant and/or researcher for Allergan, Cutera, Cynosure, Cytrellis, Kythera, Lumenis, Merz, Miramar, Sebacia, Sienna Labs, Solta, Zeltiq, and Zift.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
VIDEO: Molecular testing helps pinpoint ambiguous lesions
WAILEA, HAWAII – In a video interview, Pedram Gerami, MD, professor of dermatology, pathology, and pediatrics, Northwestern University, Chicago, discusses the use of molecular testing for melanoma and suspicious lesions.
Molecular tests are available for various components of diagnosis and prognosis of melanoma, and one of the most popular scenarios for their use is to confirm a diagnosis if a lesion is biopsied and the histopathologist “feels that the diagnosis is ambiguous by standard pathology methods,” Dr. Gerami said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
On average, between 1% and 5% of cases of suspicious lesions may need molecular testing to confirm the diagnosis, he noted. Of the available options for molecular testing, FISH (fluorescence in situ hybridization) testing is the most validated in the setting of ambiguous histology, he said.
Dr. Gerami disclosed serving as a consultant and researcher for Castle Biosciences, Myriad Genetics, and DermTech.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – In a video interview, Pedram Gerami, MD, professor of dermatology, pathology, and pediatrics, Northwestern University, Chicago, discusses the use of molecular testing for melanoma and suspicious lesions.
Molecular tests are available for various components of diagnosis and prognosis of melanoma, and one of the most popular scenarios for their use is to confirm a diagnosis if a lesion is biopsied and the histopathologist “feels that the diagnosis is ambiguous by standard pathology methods,” Dr. Gerami said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
On average, between 1% and 5% of cases of suspicious lesions may need molecular testing to confirm the diagnosis, he noted. Of the available options for molecular testing, FISH (fluorescence in situ hybridization) testing is the most validated in the setting of ambiguous histology, he said.
Dr. Gerami disclosed serving as a consultant and researcher for Castle Biosciences, Myriad Genetics, and DermTech.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAILEA, HAWAII – In a video interview, Pedram Gerami, MD, professor of dermatology, pathology, and pediatrics, Northwestern University, Chicago, discusses the use of molecular testing for melanoma and suspicious lesions.
Molecular tests are available for various components of diagnosis and prognosis of melanoma, and one of the most popular scenarios for their use is to confirm a diagnosis if a lesion is biopsied and the histopathologist “feels that the diagnosis is ambiguous by standard pathology methods,” Dr. Gerami said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
On average, between 1% and 5% of cases of suspicious lesions may need molecular testing to confirm the diagnosis, he noted. Of the available options for molecular testing, FISH (fluorescence in situ hybridization) testing is the most validated in the setting of ambiguous histology, he said.
Dr. Gerami disclosed serving as a consultant and researcher for Castle Biosciences, Myriad Genetics, and DermTech.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
