AAD Annual Meeting 2013

MIAMI BEACH – In practice, acne patients are treated three times longer than clinical trials suggest, based on data from more than 2,000 patients at an academic medical center.

The findings have implications both for setting patients’ treatment expectations and for designing future clinical trials, said Karen Huang of Wake Forest University, Winston-Salem, N.C., said at the annual meeting of the American Academy of Dermatology.

Ms. Huang and her colleagues reviewed electronic records for patients who were treated at an academic medical practice between Jan. 1, 2009, and Nov. 15, 2012. Overall, 2,250 patients had at least one acne-related visit with a dermatologist. Of these, 57% had only one visit and 43% had multiple visits.

For patients who had multiple visits, the mean duration of treatment from the first to the last visit was approximately 9 months (0.79 years). Approximately 25% continued seeing their dermatologists for about a year, and half continued treatment for nearly 5 months (0.4 years).

Not unexpectedly, patients treated with oral medication, including isotretinoin and other oral treatments, were more likely than those treated with topical medications to have multiple visits. In addition, the number of visits by patients who received isotretinoin slowed gradually at first, then declined more rapidly over time compared with patients who received topical treatments.

Approximately 90% of individuals experience acne during their lifetimes, but the actual duration of acne episodes has not been well characterized in the literature, said Ms. Huang. The duration of treatment seen in 40 recent studies of acne treatment identified at clinicaltrials.gov was about 12 weeks, she added.

The current findings represent a lower limit on the duration of acne treatment because of a lack of data on which patients may have discontinued treatment prematurely or continued treatment elsewhere, such as with a primary care physician, she said.

The study findings may be of interest not only for clinical trial design (in that researchers might want to simulate average treatment duration), but also for physicians who want to set realistic expectations about treatment for their patients.

"It has been shown that if you help set patients’ expectations of what their treatment will be like, it may help improve adherence," she said.

Ms. Huang had no financial conflicts to disclose.

MIAMI BEACH – In practice, acne patients are treated three times longer than clinical trials suggest, based on data from more than 2,000 patients at an academic medical center.

The findings have implications both for setting patients’ treatment expectations and for designing future clinical trials, said Karen Huang of Wake Forest University, Winston-Salem, N.C., said at the annual meeting of the American Academy of Dermatology.

Ms. Huang and her colleagues reviewed electronic records for patients who were treated at an academic medical practice between Jan. 1, 2009, and Nov. 15, 2012. Overall, 2,250 patients had at least one acne-related visit with a dermatologist. Of these, 57% had only one visit and 43% had multiple visits.

For patients who had multiple visits, the mean duration of treatment from the first to the last visit was approximately 9 months (0.79 years). Approximately 25% continued seeing their dermatologists for about a year, and half continued treatment for nearly 5 months (0.4 years).

Not unexpectedly, patients treated with oral medication, including isotretinoin and other oral treatments, were more likely than those treated with topical medications to have multiple visits. In addition, the number of visits by patients who received isotretinoin slowed gradually at first, then declined more rapidly over time compared with patients who received topical treatments.

Approximately 90% of individuals experience acne during their lifetimes, but the actual duration of acne episodes has not been well characterized in the literature, said Ms. Huang. The duration of treatment seen in 40 recent studies of acne treatment identified at clinicaltrials.gov was about 12 weeks, she added.

The current findings represent a lower limit on the duration of acne treatment because of a lack of data on which patients may have discontinued treatment prematurely or continued treatment elsewhere, such as with a primary care physician, she said.

The study findings may be of interest not only for clinical trial design (in that researchers might want to simulate average treatment duration), but also for physicians who want to set realistic expectations about treatment for their patients.

"It has been shown that if you help set patients’ expectations of what their treatment will be like, it may help improve adherence," she said.

Ms. Huang had no financial conflicts to disclose.

MIAMI BEACH – In practice, acne patients are treated three times longer than clinical trials suggest, based on data from more than 2,000 patients at an academic medical center.

The findings have implications both for setting patients’ treatment expectations and for designing future clinical trials, said Karen Huang of Wake Forest University, Winston-Salem, N.C., said at the annual meeting of the American Academy of Dermatology.

Ms. Huang and her colleagues reviewed electronic records for patients who were treated at an academic medical practice between Jan. 1, 2009, and Nov. 15, 2012. Overall, 2,250 patients had at least one acne-related visit with a dermatologist. Of these, 57% had only one visit and 43% had multiple visits.

For patients who had multiple visits, the mean duration of treatment from the first to the last visit was approximately 9 months (0.79 years). Approximately 25% continued seeing their dermatologists for about a year, and half continued treatment for nearly 5 months (0.4 years).

Not unexpectedly, patients treated with oral medication, including isotretinoin and other oral treatments, were more likely than those treated with topical medications to have multiple visits. In addition, the number of visits by patients who received isotretinoin slowed gradually at first, then declined more rapidly over time compared with patients who received topical treatments.

Approximately 90% of individuals experience acne during their lifetimes, but the actual duration of acne episodes has not been well characterized in the literature, said Ms. Huang. The duration of treatment seen in 40 recent studies of acne treatment identified at clinicaltrials.gov was about 12 weeks, she added.

The current findings represent a lower limit on the duration of acne treatment because of a lack of data on which patients may have discontinued treatment prematurely or continued treatment elsewhere, such as with a primary care physician, she said.

The study findings may be of interest not only for clinical trial design (in that researchers might want to simulate average treatment duration), but also for physicians who want to set realistic expectations about treatment for their patients.

"It has been shown that if you help set patients’ expectations of what their treatment will be like, it may help improve adherence," she said.

Ms. Huang had no financial conflicts to disclose.

The oral phosphodiesterase-4 inhibitor apremilast significantly improves moderate to severe psoriasis with minimal side effects, according to data from a phase III, randomized controlled trial of 844 patients.

The drug had an excellent safety profile and resulted in significantly greater improvement in moderate to severe psoriasis than placebo after 16 weeks of treatment in the ESTEEM 1 trial.

The results were reported in a late-breaker session at the annual meeting of the American Academy of Dermatology.

Apremilast is "one of the new small molecules being developed for treatment of psoriasis," said Dr. Kristian Reich of SCIderm Research Institute and Dermatologikum, Hamburg, Germany.

"We believe it has anti-inflammatory properties, because by increasing the intracellular level of cyclic AMP (adenosine monophosphate), it actually activates protein kinase A to modulate the balance between proinflammatory and anti-inflammatory mediators released by a cell in a way that pro-inflammatory mediators are down-regulated and anti-inflammatory mediators are upregulated," he said.

Of 562 patients randomized to receive 30 mg of apremilast twice daily for 16 weeks, 33.1% achieved 75% improvement on the Psoriasis Area Severity Index (PASI-75) scale score, compared with only 5.3% of 282 patients who received placebo. Patients in the treatment group also showed significant improvement compared with the placebo group for secondary endpoints including physician global assessment (PGA) score, change in body surface area affected, and pruritus.

Improvements also were noted in difficult to treat areas such as the scalp and nails. For example, about 50% of affected patients achieved a 50% reduction in nail psoriasis severity, Dr. Reich said.

The study participants were adults with moderate to severe chronic plaque psoriasis, surface area involvement greater than 10%, and a PGA score of 3 or higher. All were candidates for phototherapy or systemic therapy, half had been treated previously with other systemic therapies, including biologics, and nearly 1 in 5 patients had been treated with tumor necrosis factor (TNF) blockers.

Patients initially receiving placebo switched over to active treatment after the first 16 weeks, and treatment in all patients continued at the 30-mg twice-daily dose for an additional 16 weeks, followed by a randomized withdrawal phase through week 52.

The treatment effects seen with apremilast at 16 weeks were slightly greater in patients who had not previously received conventional systemic or biologic therapy compared with the total patient population, but even those with prior failed TNF treatment achieved a PASI-75 response.

Onset of action occurred within 2-4 weeks, and clinically relevant improvement continued beyond 16 weeks. The mean percent change from baseline in PASI score was 54.9% at 16 weeks, and 61.9% at 32 weeks, Dr. Reich said. "It will be interesting to see, long-term, what happens beyond the 16-week endpoint," he added.

The 16-week outcomes in the apremilast group represent "significant moderate efficacy," but the safety profile of the drug is the real story of the data, Dr. Reich said.

"Safety is a major issue when it comes to systemic therapies for psoriasis," he emphasized.

A slightly higher rate of withdrawals in the apremilast group may have been due to gastrointestinal effects, a well-known side effect of TNF inhibitors.

Gastrointestinal side effects included diarrhea and nausea, but most cases were transient, and mild to moderate. Most side effects occurred and resolved within the first 15 days of treatment. In fact, more than 96% of patients reported experiencing either no adverse events or only mild to moderate adverse events. Reports of serious adverse events were similar in the treatment and placebo groups (2.1% v. 2.8%, respectively), as were reports of severe adverse events (3.6% vs. 3.2%, respectively).

No problems were noted with respect to lipid levels, liver enzymes, opportunistic infections, or cardiac abnormalities, and no cases of tuberculosis or lymphoma occurred during the study period.

"What stands out so far is an extremely good safety profile," Dr. Reich said.

ESTEEM 1 is the first of two phase III studies of apremilast for chronic plaque psoriasis. Statistical significance for the primary and major secondary endpoints of both ESTEEM 1 and ESTEEM 2 was announced previously by Celgene, the maker of apremilast.

"A NDA (New Drug Application) submission to the U.S. Food and Drug Administration, based on the combined ESTEEM 1 and 2 studies for psoriasis, is expected in the second half of 2013," according to a Celgene press release.

Celgene previously announced it would file a separate NDA for psoriatic arthritis in the first quarter of 2013, based on data from three other trials (PALACE-1, 2, and 3), which were released in 2012. Another phase III trial (POSTURE) began enrolling patients in April 2012 to evaluate apremilast in patients with ankylosing spondylitis.

Participants in the ESTEEM 1 trial will be enrolled in a 5-year extension study so researchers can collect long-term safety and efficacy data. However, based on the current findings, including data from psoriatic arthritis patients, the drug looks quite promising for the treatment of psoriasis, Dr. Reich said.

"I see this as a prime candidate for future management of psoriasis that allows us to treat a range of patients, including more moderate cases earlier on," he said. Such a treatment is needed, particularly in light of new disease concepts that characterize psoriasis as involving systemic inflammation that requires early control, he explained.

The study was sponsored by Celgene.

The oral phosphodiesterase-4 inhibitor apremilast significantly improves moderate to severe psoriasis with minimal side effects, according to data from a phase III, randomized controlled trial of 844 patients.

The drug had an excellent safety profile and resulted in significantly greater improvement in moderate to severe psoriasis than placebo after 16 weeks of treatment in the ESTEEM 1 trial.

The results were reported in a late-breaker session at the annual meeting of the American Academy of Dermatology.

Apremilast is "one of the new small molecules being developed for treatment of psoriasis," said Dr. Kristian Reich of SCIderm Research Institute and Dermatologikum, Hamburg, Germany.

"We believe it has anti-inflammatory properties, because by increasing the intracellular level of cyclic AMP (adenosine monophosphate), it actually activates protein kinase A to modulate the balance between proinflammatory and anti-inflammatory mediators released by a cell in a way that pro-inflammatory mediators are down-regulated and anti-inflammatory mediators are upregulated," he said.

Of 562 patients randomized to receive 30 mg of apremilast twice daily for 16 weeks, 33.1% achieved 75% improvement on the Psoriasis Area Severity Index (PASI-75) scale score, compared with only 5.3% of 282 patients who received placebo. Patients in the treatment group also showed significant improvement compared with the placebo group for secondary endpoints including physician global assessment (PGA) score, change in body surface area affected, and pruritus.

Improvements also were noted in difficult to treat areas such as the scalp and nails. For example, about 50% of affected patients achieved a 50% reduction in nail psoriasis severity, Dr. Reich said.

The study participants were adults with moderate to severe chronic plaque psoriasis, surface area involvement greater than 10%, and a PGA score of 3 or higher. All were candidates for phototherapy or systemic therapy, half had been treated previously with other systemic therapies, including biologics, and nearly 1 in 5 patients had been treated with tumor necrosis factor (TNF) blockers.

Patients initially receiving placebo switched over to active treatment after the first 16 weeks, and treatment in all patients continued at the 30-mg twice-daily dose for an additional 16 weeks, followed by a randomized withdrawal phase through week 52.

The treatment effects seen with apremilast at 16 weeks were slightly greater in patients who had not previously received conventional systemic or biologic therapy compared with the total patient population, but even those with prior failed TNF treatment achieved a PASI-75 response.

Onset of action occurred within 2-4 weeks, and clinically relevant improvement continued beyond 16 weeks. The mean percent change from baseline in PASI score was 54.9% at 16 weeks, and 61.9% at 32 weeks, Dr. Reich said. "It will be interesting to see, long-term, what happens beyond the 16-week endpoint," he added.

The 16-week outcomes in the apremilast group represent "significant moderate efficacy," but the safety profile of the drug is the real story of the data, Dr. Reich said.

"Safety is a major issue when it comes to systemic therapies for psoriasis," he emphasized.

A slightly higher rate of withdrawals in the apremilast group may have been due to gastrointestinal effects, a well-known side effect of TNF inhibitors.

Gastrointestinal side effects included diarrhea and nausea, but most cases were transient, and mild to moderate. Most side effects occurred and resolved within the first 15 days of treatment. In fact, more than 96% of patients reported experiencing either no adverse events or only mild to moderate adverse events. Reports of serious adverse events were similar in the treatment and placebo groups (2.1% v. 2.8%, respectively), as were reports of severe adverse events (3.6% vs. 3.2%, respectively).

No problems were noted with respect to lipid levels, liver enzymes, opportunistic infections, or cardiac abnormalities, and no cases of tuberculosis or lymphoma occurred during the study period.

"What stands out so far is an extremely good safety profile," Dr. Reich said.

ESTEEM 1 is the first of two phase III studies of apremilast for chronic plaque psoriasis. Statistical significance for the primary and major secondary endpoints of both ESTEEM 1 and ESTEEM 2 was announced previously by Celgene, the maker of apremilast.

"A NDA (New Drug Application) submission to the U.S. Food and Drug Administration, based on the combined ESTEEM 1 and 2 studies for psoriasis, is expected in the second half of 2013," according to a Celgene press release.

Celgene previously announced it would file a separate NDA for psoriatic arthritis in the first quarter of 2013, based on data from three other trials (PALACE-1, 2, and 3), which were released in 2012. Another phase III trial (POSTURE) began enrolling patients in April 2012 to evaluate apremilast in patients with ankylosing spondylitis.

Participants in the ESTEEM 1 trial will be enrolled in a 5-year extension study so researchers can collect long-term safety and efficacy data. However, based on the current findings, including data from psoriatic arthritis patients, the drug looks quite promising for the treatment of psoriasis, Dr. Reich said.

"I see this as a prime candidate for future management of psoriasis that allows us to treat a range of patients, including more moderate cases earlier on," he said. Such a treatment is needed, particularly in light of new disease concepts that characterize psoriasis as involving systemic inflammation that requires early control, he explained.

The study was sponsored by Celgene.

The oral phosphodiesterase-4 inhibitor apremilast significantly improves moderate to severe psoriasis with minimal side effects, according to data from a phase III, randomized controlled trial of 844 patients.

The drug had an excellent safety profile and resulted in significantly greater improvement in moderate to severe psoriasis than placebo after 16 weeks of treatment in the ESTEEM 1 trial.

The results were reported in a late-breaker session at the annual meeting of the American Academy of Dermatology.

Apremilast is "one of the new small molecules being developed for treatment of psoriasis," said Dr. Kristian Reich of SCIderm Research Institute and Dermatologikum, Hamburg, Germany.

"We believe it has anti-inflammatory properties, because by increasing the intracellular level of cyclic AMP (adenosine monophosphate), it actually activates protein kinase A to modulate the balance between proinflammatory and anti-inflammatory mediators released by a cell in a way that pro-inflammatory mediators are down-regulated and anti-inflammatory mediators are upregulated," he said.

Of 562 patients randomized to receive 30 mg of apremilast twice daily for 16 weeks, 33.1% achieved 75% improvement on the Psoriasis Area Severity Index (PASI-75) scale score, compared with only 5.3% of 282 patients who received placebo. Patients in the treatment group also showed significant improvement compared with the placebo group for secondary endpoints including physician global assessment (PGA) score, change in body surface area affected, and pruritus.

Improvements also were noted in difficult to treat areas such as the scalp and nails. For example, about 50% of affected patients achieved a 50% reduction in nail psoriasis severity, Dr. Reich said.

The study participants were adults with moderate to severe chronic plaque psoriasis, surface area involvement greater than 10%, and a PGA score of 3 or higher. All were candidates for phototherapy or systemic therapy, half had been treated previously with other systemic therapies, including biologics, and nearly 1 in 5 patients had been treated with tumor necrosis factor (TNF) blockers.

Patients initially receiving placebo switched over to active treatment after the first 16 weeks, and treatment in all patients continued at the 30-mg twice-daily dose for an additional 16 weeks, followed by a randomized withdrawal phase through week 52.

The treatment effects seen with apremilast at 16 weeks were slightly greater in patients who had not previously received conventional systemic or biologic therapy compared with the total patient population, but even those with prior failed TNF treatment achieved a PASI-75 response.

Onset of action occurred within 2-4 weeks, and clinically relevant improvement continued beyond 16 weeks. The mean percent change from baseline in PASI score was 54.9% at 16 weeks, and 61.9% at 32 weeks, Dr. Reich said. "It will be interesting to see, long-term, what happens beyond the 16-week endpoint," he added.

The 16-week outcomes in the apremilast group represent "significant moderate efficacy," but the safety profile of the drug is the real story of the data, Dr. Reich said.

"Safety is a major issue when it comes to systemic therapies for psoriasis," he emphasized.

A slightly higher rate of withdrawals in the apremilast group may have been due to gastrointestinal effects, a well-known side effect of TNF inhibitors.

Gastrointestinal side effects included diarrhea and nausea, but most cases were transient, and mild to moderate. Most side effects occurred and resolved within the first 15 days of treatment. In fact, more than 96% of patients reported experiencing either no adverse events or only mild to moderate adverse events. Reports of serious adverse events were similar in the treatment and placebo groups (2.1% v. 2.8%, respectively), as were reports of severe adverse events (3.6% vs. 3.2%, respectively).

No problems were noted with respect to lipid levels, liver enzymes, opportunistic infections, or cardiac abnormalities, and no cases of tuberculosis or lymphoma occurred during the study period.

"What stands out so far is an extremely good safety profile," Dr. Reich said.

ESTEEM 1 is the first of two phase III studies of apremilast for chronic plaque psoriasis. Statistical significance for the primary and major secondary endpoints of both ESTEEM 1 and ESTEEM 2 was announced previously by Celgene, the maker of apremilast.

"A NDA (New Drug Application) submission to the U.S. Food and Drug Administration, based on the combined ESTEEM 1 and 2 studies for psoriasis, is expected in the second half of 2013," according to a Celgene press release.

Celgene previously announced it would file a separate NDA for psoriatic arthritis in the first quarter of 2013, based on data from three other trials (PALACE-1, 2, and 3), which were released in 2012. Another phase III trial (POSTURE) began enrolling patients in April 2012 to evaluate apremilast in patients with ankylosing spondylitis.

Participants in the ESTEEM 1 trial will be enrolled in a 5-year extension study so researchers can collect long-term safety and efficacy data. However, based on the current findings, including data from psoriatic arthritis patients, the drug looks quite promising for the treatment of psoriasis, Dr. Reich said.

"I see this as a prime candidate for future management of psoriasis that allows us to treat a range of patients, including more moderate cases earlier on," he said. Such a treatment is needed, particularly in light of new disease concepts that characterize psoriasis as involving systemic inflammation that requires early control, he explained.

The study was sponsored by Celgene.

The day before the American Academy of Dermatology’s annual meeting kicked off, more than 50 volunteer dermatologists visited the Miami Beach Police Athletic League’s Youth Resource Center, put on jeans and a t-shirt, and assembled furniture, planted trees, and painted the walls.

The Youth Center is funded mostly through donations and fundraisers, so there’s not much to go around for renovation projects.

The AAD’s volunteer event equaled close to $10,000 if the Center were to buy the item and pay for labor, said its executive director, Officer Art Martineau. "It’s just like Christmas," he said. 

This is the third year the AAD has organized the volunteer event, working with the Hands On program to identify projects in the cities where the annual meeting takes place. 

Planning the event takes time and has its costs, but for the Academy, it’s a way to give back to the community it is visiting, said AAD’s past president, Dr. William James, who has attended the annual volunteer events, starting with New Orleans.

-By Naseem S. Miller

n.miller@elsevier.com

On Twitter @naseemsmiller

The day before the American Academy of Dermatology’s annual meeting kicked off, more than 50 volunteer dermatologists visited the Miami Beach Police Athletic League’s Youth Resource Center, put on jeans and a t-shirt, and assembled furniture, planted trees, and painted the walls.

The Youth Center is funded mostly through donations and fundraisers, so there’s not much to go around for renovation projects.

The AAD’s volunteer event equaled close to $10,000 if the Center were to buy the item and pay for labor, said its executive director, Officer Art Martineau. "It’s just like Christmas," he said. 

This is the third year the AAD has organized the volunteer event, working with the Hands On program to identify projects in the cities where the annual meeting takes place. 

Planning the event takes time and has its costs, but for the Academy, it’s a way to give back to the community it is visiting, said AAD’s past president, Dr. William James, who has attended the annual volunteer events, starting with New Orleans.

-By Naseem S. Miller

n.miller@elsevier.com

On Twitter @naseemsmiller

The day before the American Academy of Dermatology’s annual meeting kicked off, more than 50 volunteer dermatologists visited the Miami Beach Police Athletic League’s Youth Resource Center, put on jeans and a t-shirt, and assembled furniture, planted trees, and painted the walls.

The Youth Center is funded mostly through donations and fundraisers, so there’s not much to go around for renovation projects.

The AAD’s volunteer event equaled close to $10,000 if the Center were to buy the item and pay for labor, said its executive director, Officer Art Martineau. "It’s just like Christmas," he said. 

This is the third year the AAD has organized the volunteer event, working with the Hands On program to identify projects in the cities where the annual meeting takes place. 

Planning the event takes time and has its costs, but for the Academy, it’s a way to give back to the community it is visiting, said AAD’s past president, Dr. William James, who has attended the annual volunteer events, starting with New Orleans.

-By Naseem S. Miller

n.miller@elsevier.com

On Twitter @naseemsmiller

MIAMI BEACH – ATX-101, an investigational injectable deoxycholic acid, is safe and effective for the non-surgical reduction of submental fat, according to interim findings from a 12-month phase IIIb open-label study.

At 3-month follow-up after their last treatment, 87% and 83% of 165 study participants achieved at least a 1-point improvement on the clinician and patient submental fat rating scales, respectively, Dr. Susan Weinkle reported during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

"That is major," Dr. Weinkle, a dermatologist in private practice in Bradenton, Fla., said of the patients’ rating scale scores.

Patients reported feeling less bothered by, and self-conscious about, their submental fat, and they also reported feeling younger. Most – about 96% – experienced unchanged or improved skin laxity in the treated area.

"Many, despite the fact that their body mass index stayed the same, actually felt like they looked like they had lost weight ... let me tell you, they were very, very happy," she said.

In fact, 94% reported being happy they had the procedure.

The study participants were men and women of varying ages, races, and Fitzpatrick skin types, who were dissatisfied with their appearance associated with the chin region. All had submental fat scale scores of 2 to 4 on both clinician and patient rating scales, had stable weight, and had received no prior treatments to the submental fat region. They received up to 6 treatments, at 4-week intervals, with ATX-101 at a dosage of 2 mg/cm². Injections were administered with a 30-gauge needle, and "little microinjections at 2 mm areas across the submental region," Dr. Weinkle said, noting that the number of injections was tailored as the fat decreased over time.

Treatments were provided at 21 sites across the United States.

Treatment-related adverse events occurred in more than 91% of patients, but these were mainly mild-to-moderate injection site hematomas, numbness, pain, edema, and erythema – and all were transient, she said

No changes in blood lipids occurred.

This "really exciting research" suggests that ATX-101, a synthetically derived product that has been shown to destroy and eliminate fat through adipocytolysis, "may very well provide, in the future, an approach to submental fat for our patients who are so unhappy with this part of their body," she said.

"This is an important thing to people, and it makes a huge difference ... if [ATX-101] has the opportunity to come to market, it will make a big impact for our patients," she added.

To date, between 2,000 and 3,000 patients have been studied, including 1,500 who have received active treatment, and 1,500 who received placebo. Patients in the current study will be followed out to 12 months, she said.

This study was funded by Kythera. Dr. Weinkle disclosed that she worked with Kythera as an investigator for the study.

MIAMI BEACH – ATX-101, an investigational injectable deoxycholic acid, is safe and effective for the non-surgical reduction of submental fat, according to interim findings from a 12-month phase IIIb open-label study.

At 3-month follow-up after their last treatment, 87% and 83% of 165 study participants achieved at least a 1-point improvement on the clinician and patient submental fat rating scales, respectively, Dr. Susan Weinkle reported during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

"That is major," Dr. Weinkle, a dermatologist in private practice in Bradenton, Fla., said of the patients’ rating scale scores.

Patients reported feeling less bothered by, and self-conscious about, their submental fat, and they also reported feeling younger. Most – about 96% – experienced unchanged or improved skin laxity in the treated area.

"Many, despite the fact that their body mass index stayed the same, actually felt like they looked like they had lost weight ... let me tell you, they were very, very happy," she said.

In fact, 94% reported being happy they had the procedure.

The study participants were men and women of varying ages, races, and Fitzpatrick skin types, who were dissatisfied with their appearance associated with the chin region. All had submental fat scale scores of 2 to 4 on both clinician and patient rating scales, had stable weight, and had received no prior treatments to the submental fat region. They received up to 6 treatments, at 4-week intervals, with ATX-101 at a dosage of 2 mg/cm². Injections were administered with a 30-gauge needle, and "little microinjections at 2 mm areas across the submental region," Dr. Weinkle said, noting that the number of injections was tailored as the fat decreased over time.

Treatments were provided at 21 sites across the United States.

Treatment-related adverse events occurred in more than 91% of patients, but these were mainly mild-to-moderate injection site hematomas, numbness, pain, edema, and erythema – and all were transient, she said

No changes in blood lipids occurred.

This "really exciting research" suggests that ATX-101, a synthetically derived product that has been shown to destroy and eliminate fat through adipocytolysis, "may very well provide, in the future, an approach to submental fat for our patients who are so unhappy with this part of their body," she said.

"This is an important thing to people, and it makes a huge difference ... if [ATX-101] has the opportunity to come to market, it will make a big impact for our patients," she added.

To date, between 2,000 and 3,000 patients have been studied, including 1,500 who have received active treatment, and 1,500 who received placebo. Patients in the current study will be followed out to 12 months, she said.

This study was funded by Kythera. Dr. Weinkle disclosed that she worked with Kythera as an investigator for the study.

MIAMI BEACH – ATX-101, an investigational injectable deoxycholic acid, is safe and effective for the non-surgical reduction of submental fat, according to interim findings from a 12-month phase IIIb open-label study.

At 3-month follow-up after their last treatment, 87% and 83% of 165 study participants achieved at least a 1-point improvement on the clinician and patient submental fat rating scales, respectively, Dr. Susan Weinkle reported during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

"That is major," Dr. Weinkle, a dermatologist in private practice in Bradenton, Fla., said of the patients’ rating scale scores.

Patients reported feeling less bothered by, and self-conscious about, their submental fat, and they also reported feeling younger. Most – about 96% – experienced unchanged or improved skin laxity in the treated area.

"Many, despite the fact that their body mass index stayed the same, actually felt like they looked like they had lost weight ... let me tell you, they were very, very happy," she said.

In fact, 94% reported being happy they had the procedure.

The study participants were men and women of varying ages, races, and Fitzpatrick skin types, who were dissatisfied with their appearance associated with the chin region. All had submental fat scale scores of 2 to 4 on both clinician and patient rating scales, had stable weight, and had received no prior treatments to the submental fat region. They received up to 6 treatments, at 4-week intervals, with ATX-101 at a dosage of 2 mg/cm². Injections were administered with a 30-gauge needle, and "little microinjections at 2 mm areas across the submental region," Dr. Weinkle said, noting that the number of injections was tailored as the fat decreased over time.

Treatments were provided at 21 sites across the United States.

Treatment-related adverse events occurred in more than 91% of patients, but these were mainly mild-to-moderate injection site hematomas, numbness, pain, edema, and erythema – and all were transient, she said

No changes in blood lipids occurred.

This "really exciting research" suggests that ATX-101, a synthetically derived product that has been shown to destroy and eliminate fat through adipocytolysis, "may very well provide, in the future, an approach to submental fat for our patients who are so unhappy with this part of their body," she said.

"This is an important thing to people, and it makes a huge difference ... if [ATX-101] has the opportunity to come to market, it will make a big impact for our patients," she added.

To date, between 2,000 and 3,000 patients have been studied, including 1,500 who have received active treatment, and 1,500 who received placebo. Patients in the current study will be followed out to 12 months, she said.

This study was funded by Kythera. Dr. Weinkle disclosed that she worked with Kythera as an investigator for the study.

MIAMI BEACH – ICD-11 is a better classification system for skin diseases and dermatologists should take the time now to help shape its final form.

For the 11th revision of the International Classification of Diseases, the chapter on skin diseases has been completely redesigned, said Dr. Robert J. G. Chalmers, co-chair and managing editor of the Dermatology Topic Advisory Group for ICD-11.

Now in its beta version, ICD-11 is assembled as a Wiki-like knowledge base: Its building blocks are "concepts," which may refer to a single disease, disorder or syndrome, or to a group of related disorders.

Each concept will have terms, explicit inclusion and exclusion rules, and hierarchical links to its "parents," "siblings," and "children."

The skin diseases chapter will have 21 major headings, each of which is subdivided into logical groupings and sub-groupings, Dr. Chalmers said at the annual meeting of the American Academy of Dermatology.

Unlike in ICD-10 – slated to be adopted in the United States next year – the web-based view of ICD-11 allows any one concept to have more than one logical parent. For instance, erythema nodosum leprosum can be displayed both as a form of cutaneous vasculitis and as a complication of leprosy. This "polyhierarchy" also enables diseases such as cutaneous infections and neoplasms to be displayed within the skin chapter even though their preferred location may reside within a different chapter.

The revisions will help dermatologists to better document diseases, care for their patients, and assist recruitment for clinical trials. "It’s a better way of capturing information," said Dr. Chalmers.

The ICD was first published in the late 1890s, and included a total of four codes for skin diseases: ulcer, bed-sore; eczema; pemphigus; and other diseases of the skin. But by the 5th edition, eczema and pemphigus had disappeared from the codes, leaving only carbuncle and boils; cellulitis, acute abscess and other diseases of the skin and cellular tissue, Dr. Chalmers said.

ICD-6, which was published in 1948, was entrusted to the newly-formed World Health Organization which continues to publish the code sets.

The 6th edition contained 60 skin diseases, but very little changed from that version until ICD-9, published in 1975.

ICD-9 is still used in the United States, and ICD-10, which was published in 1990 and introduced into clinical practice some 20 years ago in much of the world, is set to replace ICD-9 in the United States next year. The two versions are very similar and "for a dermatologist, ICD-10 remains crude and cumbersome instrument full of bizarre inconsistencies," said Dr. Chalmers, a consultant dermatologist at the University of Manchester, United Kingdom.

Plans for ICD-11 were announced by the WHO in 2007, and the revision is set for release in 2015.

Dr. Chalmers said that it will probably be at least 5 years from now before ICD-11 is available for clinical use. But given the timeline for implementation of ICD-10 in the United States, he said there is no telling when ICD-11 will be available here.

U.S. doctors have challenged the adoption of ICD-10 for several reasons such as having to establish new billing and collection systems, a need for staff training, and an expectation of lower reimbursement.

The American Academy of Dermatology Association, along with the American Medical Association, have urged the Centers for Medicare and Medicaid Services to skip over ICD-10 and wait to update the code set until ICD-11 becomes available. Their request has been declined.

In the meantime, Dr. Chalmers encouraged dermatologists to visit the ICD-11 beta version and share comments, proposals, and definitions, and to participate in field trials.

Dr. Chalmers had no relationships to disclose.

MIAMI BEACH – ICD-11 is a better classification system for skin diseases and dermatologists should take the time now to help shape its final form.

For the 11th revision of the International Classification of Diseases, the chapter on skin diseases has been completely redesigned, said Dr. Robert J. G. Chalmers, co-chair and managing editor of the Dermatology Topic Advisory Group for ICD-11.

Now in its beta version, ICD-11 is assembled as a Wiki-like knowledge base: Its building blocks are "concepts," which may refer to a single disease, disorder or syndrome, or to a group of related disorders.

Each concept will have terms, explicit inclusion and exclusion rules, and hierarchical links to its "parents," "siblings," and "children."

The skin diseases chapter will have 21 major headings, each of which is subdivided into logical groupings and sub-groupings, Dr. Chalmers said at the annual meeting of the American Academy of Dermatology.

Unlike in ICD-10 – slated to be adopted in the United States next year – the web-based view of ICD-11 allows any one concept to have more than one logical parent. For instance, erythema nodosum leprosum can be displayed both as a form of cutaneous vasculitis and as a complication of leprosy. This "polyhierarchy" also enables diseases such as cutaneous infections and neoplasms to be displayed within the skin chapter even though their preferred location may reside within a different chapter.

The revisions will help dermatologists to better document diseases, care for their patients, and assist recruitment for clinical trials. "It’s a better way of capturing information," said Dr. Chalmers.

The ICD was first published in the late 1890s, and included a total of four codes for skin diseases: ulcer, bed-sore; eczema; pemphigus; and other diseases of the skin. But by the 5th edition, eczema and pemphigus had disappeared from the codes, leaving only carbuncle and boils; cellulitis, acute abscess and other diseases of the skin and cellular tissue, Dr. Chalmers said.

ICD-6, which was published in 1948, was entrusted to the newly-formed World Health Organization which continues to publish the code sets.

The 6th edition contained 60 skin diseases, but very little changed from that version until ICD-9, published in 1975.

ICD-9 is still used in the United States, and ICD-10, which was published in 1990 and introduced into clinical practice some 20 years ago in much of the world, is set to replace ICD-9 in the United States next year. The two versions are very similar and "for a dermatologist, ICD-10 remains crude and cumbersome instrument full of bizarre inconsistencies," said Dr. Chalmers, a consultant dermatologist at the University of Manchester, United Kingdom.

Plans for ICD-11 were announced by the WHO in 2007, and the revision is set for release in 2015.

Dr. Chalmers said that it will probably be at least 5 years from now before ICD-11 is available for clinical use. But given the timeline for implementation of ICD-10 in the United States, he said there is no telling when ICD-11 will be available here.

U.S. doctors have challenged the adoption of ICD-10 for several reasons such as having to establish new billing and collection systems, a need for staff training, and an expectation of lower reimbursement.

The American Academy of Dermatology Association, along with the American Medical Association, have urged the Centers for Medicare and Medicaid Services to skip over ICD-10 and wait to update the code set until ICD-11 becomes available. Their request has been declined.

In the meantime, Dr. Chalmers encouraged dermatologists to visit the ICD-11 beta version and share comments, proposals, and definitions, and to participate in field trials.

Dr. Chalmers had no relationships to disclose.

MIAMI BEACH – ICD-11 is a better classification system for skin diseases and dermatologists should take the time now to help shape its final form.

For the 11th revision of the International Classification of Diseases, the chapter on skin diseases has been completely redesigned, said Dr. Robert J. G. Chalmers, co-chair and managing editor of the Dermatology Topic Advisory Group for ICD-11.

Now in its beta version, ICD-11 is assembled as a Wiki-like knowledge base: Its building blocks are "concepts," which may refer to a single disease, disorder or syndrome, or to a group of related disorders.

Each concept will have terms, explicit inclusion and exclusion rules, and hierarchical links to its "parents," "siblings," and "children."

The skin diseases chapter will have 21 major headings, each of which is subdivided into logical groupings and sub-groupings, Dr. Chalmers said at the annual meeting of the American Academy of Dermatology.

Unlike in ICD-10 – slated to be adopted in the United States next year – the web-based view of ICD-11 allows any one concept to have more than one logical parent. For instance, erythema nodosum leprosum can be displayed both as a form of cutaneous vasculitis and as a complication of leprosy. This "polyhierarchy" also enables diseases such as cutaneous infections and neoplasms to be displayed within the skin chapter even though their preferred location may reside within a different chapter.

The revisions will help dermatologists to better document diseases, care for their patients, and assist recruitment for clinical trials. "It’s a better way of capturing information," said Dr. Chalmers.

The ICD was first published in the late 1890s, and included a total of four codes for skin diseases: ulcer, bed-sore; eczema; pemphigus; and other diseases of the skin. But by the 5th edition, eczema and pemphigus had disappeared from the codes, leaving only carbuncle and boils; cellulitis, acute abscess and other diseases of the skin and cellular tissue, Dr. Chalmers said.

ICD-6, which was published in 1948, was entrusted to the newly-formed World Health Organization which continues to publish the code sets.

The 6th edition contained 60 skin diseases, but very little changed from that version until ICD-9, published in 1975.

ICD-9 is still used in the United States, and ICD-10, which was published in 1990 and introduced into clinical practice some 20 years ago in much of the world, is set to replace ICD-9 in the United States next year. The two versions are very similar and "for a dermatologist, ICD-10 remains crude and cumbersome instrument full of bizarre inconsistencies," said Dr. Chalmers, a consultant dermatologist at the University of Manchester, United Kingdom.

Plans for ICD-11 were announced by the WHO in 2007, and the revision is set for release in 2015.

Dr. Chalmers said that it will probably be at least 5 years from now before ICD-11 is available for clinical use. But given the timeline for implementation of ICD-10 in the United States, he said there is no telling when ICD-11 will be available here.

U.S. doctors have challenged the adoption of ICD-10 for several reasons such as having to establish new billing and collection systems, a need for staff training, and an expectation of lower reimbursement.

The American Academy of Dermatology Association, along with the American Medical Association, have urged the Centers for Medicare and Medicaid Services to skip over ICD-10 and wait to update the code set until ICD-11 becomes available. Their request has been declined.

In the meantime, Dr. Chalmers encouraged dermatologists to visit the ICD-11 beta version and share comments, proposals, and definitions, and to participate in field trials.

Dr. Chalmers had no relationships to disclose.

The increasing use of methylisothiazolinone by itself in cosmetic and toiletry products has earned the preservative the title of contact allergen of the year from the American Contact Dermatitis Society.

Methylisothiazolinone (MI), a moderate-strong sensitizer, is important to know about, because a few years ago it was introduced into the market as a stand-alone preservative at up to 100 parts per million, Dr. Donald V. Belsito, professor of clinical dermatology at Columbia University, N.Y., said at the society’s annual meeting.

Previously, MI was used only in combination with methylchloroisothiazolinone (MCI), and the concentration limit of MI in that combination was 3.75 ppm for rinse-off products, and 1.8 ppm for leave-on products. Even at those lower limits, the MCI/MI combination in 2009-2010 was considered the fifth most common cause of preservative allergy.

The new 100-ppm limit (instituted based on the belief that MI was a weaker sensitizer than MCI) represents a 25-fold increase in the permitted concentration in cosmetics, Dr. Belsito noted.

At least one study, however, has shown that the eliciting concentration for MI reactivity can be as low as 5 ppm, Dr. Mari Paz Castanedo-Tardana of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. Kathryn A. Zug of Geisel School of Medicine at Dartmouth, Hanover, N.H., noted in an article in the January/February issue of Dermatitis, which granted MI its dubious 2013 title.

Dr. Castanedo-Tardana and Dr. Zug noted that in 2010, data suggested that more than 2,400 U.S. cosmetic products contained MI, which represents a doubling since 2007. The preservative is also used in industrial products without limit, thus providing other opportunities for exposure, such as occupational exposure (Dermatitis 2013;24:1-6).

An important problem is that few data exist concerning the cross-reaction patterns of MCI and MI, the authors noted.

"Bruze et al. showed that a small proportion of patch test subjects sensitized to MCI/MI also reacted to MI. Isaksson et al. also suggested that patients with high patch test reactivity to MCI may also react to high concentrations of MI (1,000 ppm). The percentage of concomitant reactions between MCI/MI and MI in the patch test population is relevant with regard to the diagnosis of MI contact allergy," according to the authors. They also noted that in a Danish study, a Finnish study, and a German study, only 40%, 66%, and 67% of patients with a positive reaction to MI, respectively, also had a positive reaction to MCI/MI.

The limited experience with MI-only patch tests concentrations also helped the allergen gain its newly bestowed title.

Concentrations of 300 ppm (0.03% aq), 500 ppm (0.05% aq), 1,000 ppm (0.1% aq), and 2,000 ppm (0.2% aq) have been tested, and all have yielded relatively similar percentages of positive test reactions.

"As with any other allergen, the ideal patch test concentration should be able to detect as many cases of contact allergy as possible without causing irritant reactions or active sensitization," the authors said, noting that preliminary results from Denmark suggest that 2,000 ppm (0.2% aq) is an appropriate concentration.

For now, however, it is likely that since MI is not routinely tested in any standard screening series, allergy to this preservative is being widely overlooked.

In fact, reports from Europe show that the frequency of allergy to MI is already at the same level as other preservatives that have been available for many years.

"Methylisothiazolinone should be considered as a potential suspect allergen among patients with suspected cosmetic dermatitis, facial dermatitis, and sunscreen allergy," the authors said, concluding that the addition of MI to an allergen screening series "will likely uncover otherwise undiagnosed cases of preservative contact allergy."

The presenter and authors reported having no disclosures.

sknews@elsevier.com

The increasing use of methylisothiazolinone by itself in cosmetic and toiletry products has earned the preservative the title of contact allergen of the year from the American Contact Dermatitis Society.

Methylisothiazolinone (MI), a moderate-strong sensitizer, is important to know about, because a few years ago it was introduced into the market as a stand-alone preservative at up to 100 parts per million, Dr. Donald V. Belsito, professor of clinical dermatology at Columbia University, N.Y., said at the society’s annual meeting.

Previously, MI was used only in combination with methylchloroisothiazolinone (MCI), and the concentration limit of MI in that combination was 3.75 ppm for rinse-off products, and 1.8 ppm for leave-on products. Even at those lower limits, the MCI/MI combination in 2009-2010 was considered the fifth most common cause of preservative allergy.

The new 100-ppm limit (instituted based on the belief that MI was a weaker sensitizer than MCI) represents a 25-fold increase in the permitted concentration in cosmetics, Dr. Belsito noted.

At least one study, however, has shown that the eliciting concentration for MI reactivity can be as low as 5 ppm, Dr. Mari Paz Castanedo-Tardana of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. Kathryn A. Zug of Geisel School of Medicine at Dartmouth, Hanover, N.H., noted in an article in the January/February issue of Dermatitis, which granted MI its dubious 2013 title.

Dr. Castanedo-Tardana and Dr. Zug noted that in 2010, data suggested that more than 2,400 U.S. cosmetic products contained MI, which represents a doubling since 2007. The preservative is also used in industrial products without limit, thus providing other opportunities for exposure, such as occupational exposure (Dermatitis 2013;24:1-6).

An important problem is that few data exist concerning the cross-reaction patterns of MCI and MI, the authors noted.

"Bruze et al. showed that a small proportion of patch test subjects sensitized to MCI/MI also reacted to MI. Isaksson et al. also suggested that patients with high patch test reactivity to MCI may also react to high concentrations of MI (1,000 ppm). The percentage of concomitant reactions between MCI/MI and MI in the patch test population is relevant with regard to the diagnosis of MI contact allergy," according to the authors. They also noted that in a Danish study, a Finnish study, and a German study, only 40%, 66%, and 67% of patients with a positive reaction to MI, respectively, also had a positive reaction to MCI/MI.

The limited experience with MI-only patch tests concentrations also helped the allergen gain its newly bestowed title.

Concentrations of 300 ppm (0.03% aq), 500 ppm (0.05% aq), 1,000 ppm (0.1% aq), and 2,000 ppm (0.2% aq) have been tested, and all have yielded relatively similar percentages of positive test reactions.

"As with any other allergen, the ideal patch test concentration should be able to detect as many cases of contact allergy as possible without causing irritant reactions or active sensitization," the authors said, noting that preliminary results from Denmark suggest that 2,000 ppm (0.2% aq) is an appropriate concentration.

For now, however, it is likely that since MI is not routinely tested in any standard screening series, allergy to this preservative is being widely overlooked.

In fact, reports from Europe show that the frequency of allergy to MI is already at the same level as other preservatives that have been available for many years.

"Methylisothiazolinone should be considered as a potential suspect allergen among patients with suspected cosmetic dermatitis, facial dermatitis, and sunscreen allergy," the authors said, concluding that the addition of MI to an allergen screening series "will likely uncover otherwise undiagnosed cases of preservative contact allergy."

The presenter and authors reported having no disclosures.

sknews@elsevier.com

The increasing use of methylisothiazolinone by itself in cosmetic and toiletry products has earned the preservative the title of contact allergen of the year from the American Contact Dermatitis Society.

Methylisothiazolinone (MI), a moderate-strong sensitizer, is important to know about, because a few years ago it was introduced into the market as a stand-alone preservative at up to 100 parts per million, Dr. Donald V. Belsito, professor of clinical dermatology at Columbia University, N.Y., said at the society’s annual meeting.

Previously, MI was used only in combination with methylchloroisothiazolinone (MCI), and the concentration limit of MI in that combination was 3.75 ppm for rinse-off products, and 1.8 ppm for leave-on products. Even at those lower limits, the MCI/MI combination in 2009-2010 was considered the fifth most common cause of preservative allergy.

The new 100-ppm limit (instituted based on the belief that MI was a weaker sensitizer than MCI) represents a 25-fold increase in the permitted concentration in cosmetics, Dr. Belsito noted.

At least one study, however, has shown that the eliciting concentration for MI reactivity can be as low as 5 ppm, Dr. Mari Paz Castanedo-Tardana of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and Dr. Kathryn A. Zug of Geisel School of Medicine at Dartmouth, Hanover, N.H., noted in an article in the January/February issue of Dermatitis, which granted MI its dubious 2013 title.

Dr. Castanedo-Tardana and Dr. Zug noted that in 2010, data suggested that more than 2,400 U.S. cosmetic products contained MI, which represents a doubling since 2007. The preservative is also used in industrial products without limit, thus providing other opportunities for exposure, such as occupational exposure (Dermatitis 2013;24:1-6).

An important problem is that few data exist concerning the cross-reaction patterns of MCI and MI, the authors noted.

"Bruze et al. showed that a small proportion of patch test subjects sensitized to MCI/MI also reacted to MI. Isaksson et al. also suggested that patients with high patch test reactivity to MCI may also react to high concentrations of MI (1,000 ppm). The percentage of concomitant reactions between MCI/MI and MI in the patch test population is relevant with regard to the diagnosis of MI contact allergy," according to the authors. They also noted that in a Danish study, a Finnish study, and a German study, only 40%, 66%, and 67% of patients with a positive reaction to MI, respectively, also had a positive reaction to MCI/MI.

The limited experience with MI-only patch tests concentrations also helped the allergen gain its newly bestowed title.

Concentrations of 300 ppm (0.03% aq), 500 ppm (0.05% aq), 1,000 ppm (0.1% aq), and 2,000 ppm (0.2% aq) have been tested, and all have yielded relatively similar percentages of positive test reactions.

"As with any other allergen, the ideal patch test concentration should be able to detect as many cases of contact allergy as possible without causing irritant reactions or active sensitization," the authors said, noting that preliminary results from Denmark suggest that 2,000 ppm (0.2% aq) is an appropriate concentration.

For now, however, it is likely that since MI is not routinely tested in any standard screening series, allergy to this preservative is being widely overlooked.

In fact, reports from Europe show that the frequency of allergy to MI is already at the same level as other preservatives that have been available for many years.

"Methylisothiazolinone should be considered as a potential suspect allergen among patients with suspected cosmetic dermatitis, facial dermatitis, and sunscreen allergy," the authors said, concluding that the addition of MI to an allergen screening series "will likely uncover otherwise undiagnosed cases of preservative contact allergy."

The presenter and authors reported having no disclosures.

sknews@elsevier.com