MDedge Dermatology

SAN DIEGO – If approved, a novel topical gel that combines an antibiotic, an antibacterial, and a retinoid would mark an important advance for many patients with moderate-to-severe acne, according to Lawrence F. Eichenfield, MD.

The product, known as IDP-126 and being developed by Ortho Dermatologics, is a fixed dose triple combination of clindamycin 1.2% plus benzoyl peroxide 3.1% and adapalene 0.15% being evaluated in patients nine years of age and older. According to a 2021 press release from the company, results from a second 12-week pivotal phase 3 trial showed a treatment success of 50.5% and 20.5% for IDP-126 and its vehicle, respectively, along with significant changes from baseline in inflammatory lesion count and non-inflammatory lesion count.

olavs/Thinkstock

More recently, researchers led by Linda Stein Gold, MD, conducted a 12-week multicenter, randomized, double-blind study of IDP-126 in 741 children, adolescents, and adults with moderate to severe acne. They reported 52.5% of patients treated with IDP-126 gel achieved treatment success by week 12, with over 70% reduction in inflammatory and noninflammatory lesions.

“This will be interesting to follow as it moves along,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said at the annual Masters of Aesthetics Symposium in a presentation on the newest topical acne treatments.

“If approved, we probably will be able to decrease our need for systemic therapies in some individuals,” he said. “It’s something that may become important in practices that mix and match between medical and procedural or surgical approaches to acne.”

Dr. Eichenfield highlighted other products for the topical treatment of acne:

• Trifarotene cream 0.005% (Aklief). In 2019, Food and Drug Administration approval made trifarotene cream the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients age 9 and older and has been studied in acne of the face, chest, and back.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “Many of the new acne products come with a background of vehicle delivery systems that minimize the concentration gradient, so it decreases irritation,” said Dr. Eichenfield, one of the authors of a 2021 review article on the management of acne vulgaris in JAMA. “This has very good efficacy without the traditional irritation of other tazarotene products,” Dr. Eichenfield said.
• Minocycline 4% topical foam (Amzeeq). The 2019 U.S. approval marked the first and so far only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “It’s generally well tolerated.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor is approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It is safe for use in men, has been studied on the face and trunk, and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” Dr. Eichenfield said.
• Micro-encapsulated benzoyl peroxide 3% and tretinoin 0.1% cream (Twyneo). This is a once-daily fixed-dose combination of tretinoin and benzoyl peroxide indicated for the treatment of acne vulgaris in patients age 9 and older. According to a press release from Sol-Gel, the manufacturer, silica (silicon dioxide) core shell structures separate micro-encapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the two active ingredients in the cream.

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics.

SAN DIEGO – If approved, a novel topical gel that combines an antibiotic, an antibacterial, and a retinoid would mark an important advance for many patients with moderate-to-severe acne, according to Lawrence F. Eichenfield, MD.

The product, known as IDP-126 and being developed by Ortho Dermatologics, is a fixed dose triple combination of clindamycin 1.2% plus benzoyl peroxide 3.1% and adapalene 0.15% being evaluated in patients nine years of age and older. According to a 2021 press release from the company, results from a second 12-week pivotal phase 3 trial showed a treatment success of 50.5% and 20.5% for IDP-126 and its vehicle, respectively, along with significant changes from baseline in inflammatory lesion count and non-inflammatory lesion count.

olavs/Thinkstock

More recently, researchers led by Linda Stein Gold, MD, conducted a 12-week multicenter, randomized, double-blind study of IDP-126 in 741 children, adolescents, and adults with moderate to severe acne. They reported 52.5% of patients treated with IDP-126 gel achieved treatment success by week 12, with over 70% reduction in inflammatory and noninflammatory lesions.

“This will be interesting to follow as it moves along,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said at the annual Masters of Aesthetics Symposium in a presentation on the newest topical acne treatments.

“If approved, we probably will be able to decrease our need for systemic therapies in some individuals,” he said. “It’s something that may become important in practices that mix and match between medical and procedural or surgical approaches to acne.”

Dr. Eichenfield highlighted other products for the topical treatment of acne:

• Trifarotene cream 0.005% (Aklief). In 2019, Food and Drug Administration approval made trifarotene cream the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients age 9 and older and has been studied in acne of the face, chest, and back.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “Many of the new acne products come with a background of vehicle delivery systems that minimize the concentration gradient, so it decreases irritation,” said Dr. Eichenfield, one of the authors of a 2021 review article on the management of acne vulgaris in JAMA. “This has very good efficacy without the traditional irritation of other tazarotene products,” Dr. Eichenfield said.
• Minocycline 4% topical foam (Amzeeq). The 2019 U.S. approval marked the first and so far only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “It’s generally well tolerated.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor is approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It is safe for use in men, has been studied on the face and trunk, and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” Dr. Eichenfield said.
• Micro-encapsulated benzoyl peroxide 3% and tretinoin 0.1% cream (Twyneo). This is a once-daily fixed-dose combination of tretinoin and benzoyl peroxide indicated for the treatment of acne vulgaris in patients age 9 and older. According to a press release from Sol-Gel, the manufacturer, silica (silicon dioxide) core shell structures separate micro-encapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the two active ingredients in the cream.

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics.

SAN DIEGO – If approved, a novel topical gel that combines an antibiotic, an antibacterial, and a retinoid would mark an important advance for many patients with moderate-to-severe acne, according to Lawrence F. Eichenfield, MD.

The product, known as IDP-126 and being developed by Ortho Dermatologics, is a fixed dose triple combination of clindamycin 1.2% plus benzoyl peroxide 3.1% and adapalene 0.15% being evaluated in patients nine years of age and older. According to a 2021 press release from the company, results from a second 12-week pivotal phase 3 trial showed a treatment success of 50.5% and 20.5% for IDP-126 and its vehicle, respectively, along with significant changes from baseline in inflammatory lesion count and non-inflammatory lesion count.

olavs/Thinkstock

More recently, researchers led by Linda Stein Gold, MD, conducted a 12-week multicenter, randomized, double-blind study of IDP-126 in 741 children, adolescents, and adults with moderate to severe acne. They reported 52.5% of patients treated with IDP-126 gel achieved treatment success by week 12, with over 70% reduction in inflammatory and noninflammatory lesions.

“This will be interesting to follow as it moves along,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said at the annual Masters of Aesthetics Symposium in a presentation on the newest topical acne treatments.

“If approved, we probably will be able to decrease our need for systemic therapies in some individuals,” he said. “It’s something that may become important in practices that mix and match between medical and procedural or surgical approaches to acne.”

Dr. Eichenfield highlighted other products for the topical treatment of acne:

• Trifarotene cream 0.005% (Aklief). In 2019, Food and Drug Administration approval made trifarotene cream the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients age 9 and older and has been studied in acne of the face, chest, and back.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “Many of the new acne products come with a background of vehicle delivery systems that minimize the concentration gradient, so it decreases irritation,” said Dr. Eichenfield, one of the authors of a 2021 review article on the management of acne vulgaris in JAMA. “This has very good efficacy without the traditional irritation of other tazarotene products,” Dr. Eichenfield said.
• Minocycline 4% topical foam (Amzeeq). The 2019 U.S. approval marked the first and so far only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “It’s generally well tolerated.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor is approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It is safe for use in men, has been studied on the face and trunk, and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” Dr. Eichenfield said.
• Micro-encapsulated benzoyl peroxide 3% and tretinoin 0.1% cream (Twyneo). This is a once-daily fixed-dose combination of tretinoin and benzoyl peroxide indicated for the treatment of acne vulgaris in patients age 9 and older. According to a press release from Sol-Gel, the manufacturer, silica (silicon dioxide) core shell structures separate micro-encapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the two active ingredients in the cream.

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Galderma, and Ortho Dermatologics.

With the introduction of the first US Food and Drug Administration (FDA)–approved medication for alopecia areata (AA)—the Janus kinase (JAK) inhibitor, baricitinib—there is an important focus on this disease in the literature and for practicing dermatologists. Known by all as an autoimmune genetic disease that causes relapsing and remitting nonscarring hair loss, AA is a condition where the psychological burden has been less widely recognized. Patients with AA have reported lower health-related quality of life scores compared to patients with other skin conditions, including psoriasis or atopic dermatitis. In addition, a lesser amount of scalp coverage is negatively correlated to health-related quality of life scores.¹ Patients with AA also have a 39% lifetime prevalence of major depressive disorder and generalized anxiety disorder.² The treatment of AA has been a hodgepodge of topical, intralesional, and systemic agents, all with indirect immunosuppressive or anagen prolongation effects. Now that there is an approved therapy for AA with more treatments likely to be approved in the near future, there must be a focus on real-world outcomes. With the dawn of a new era in the treatment of AA as well as new information showcasing an altered prevalence of AA in skin of color, highlighting disparities among this population may help ease challenges dermatologic providers will face.

Efficacy of Baricitinib in Different Races and Ethnicities

How will patients of different races and ethnicities respond to this new treatment, and how will their emotional health be affected? The 2 phase 3 pivotal trials showing efficacy of baricitinib in AA included Black and Latino patients but not in a way that is representative of the US population.³ Until recently, the most commonly used prevalence of AA in the United States was from the NHANES I study completed between 1971 and 1974, which was between 0.1% and 0.2%⁴ with minimal focus on race and ethnicity. Recent studies suggest that there may be increased prevalence of this condition in Black patients in the United States. These new findings raise concern around access to care and treatment and the need to tailor psychosocial interventions for populations that may not currently have these supports.

A large cross-sectional study published in 2020 demonstrated that these data remained similar, with a lifetime prevalence of 0.21%.⁵ Of the 45,016 participants—representative of the US population based on the 2015 US Census—the average age of AA patients was 41.2 years, with 61.3% being White and not of Hispanic origin.⁵ In recent years, other studies have challenged the narrative that AA predominantly affects White patients.^6-8 A different cross-sectional study utilizing National Alopecia Areata Registry data from 2002 to 2016 suggested that Black patients have greater odds of developing AA.⁶ In this study of 2645 cases of AA, the odds ratios of developing the condition were 1.36 for Blacks, 0.53 for Asians, and 0.83 for Hispanics compared with the referent White population. These results were consistent through the varying subtypes of AA.⁶ In a reply to these findings, Gonzalez and Fleischer⁷ analyzed data from the 2007 to 2016 National Ambulatory Medical Care Survey database with a focus on racial and ethnic prevalence of AA. This study concluded that Latino and non-White individuals had an increased likelihood of clinician visits for AA compared with White individuals.⁷

More evidence of the Black predominance of AA was demonstrated in a study published in 2018. In this large-scale study, 63,960 women from the Nurses’ Health Study (NHS) and 88,368 women from the Nurses’ Health Study II (NHSII) were included to examine prevalence of disease among these US women.⁸ Analysis showed increased odds of AA based on self-reported race in Black and Hispanic women. Lifetime incidence of AA was greater in Black women, with 2.63 and 5.23 in NHS and NHSII, respectively. It was hypothesized that hairstyling practices in Black and Hispanic women may cause AA to be more noticeable,⁸ which may drive patients to seek medical evaluation.

Feaster and McMichael⁹ published information on the epidemiology of AA in a busy hair loss clinic. This retrospective single-institution study of 265 pediatric and adult Black patients with AA seen over a 5-year period showed that patients aged 18 to 34 years were most likely to present for care, which accounted for 35.8% of the study population, followed by patients aged 10 to 17 years, which accounted for 15.1%. This study also found that females were the larger segment of AA patients, with an increased distribution of disease in young patients. Most of these patients (68.2%) had patchy hair loss, and the ophiasis pattern was seen in 15.1%.⁹ Although the pathogenesis of AA is linked to autoimmunity,¹⁰ the leading cause for these epidemiologic findings of increased prevalence in Black patients is still uncertain.

Baricitinib for AA

In June 2022, the FDA announced the first biologic drug approved for the treatment of AA—baricitinib. Baricitinib is an oral, selective, reversible inhibitor of JAK1 and JAK2.³ The phase 3 trials for baricitinib—BRAVE-AA1 (N=654) and BRAVE-AA2 (N=546)—were conducted between March 2019 and May 2020. In these double-blind, parallel-group, randomized, placebo-controlled trials, 33% of the patient population receiving baricitinib accomplished 80% or more scalp coverage at 36 weeks. The Severity of Alopecia Tool (SALT) score also decreased to 20 or less in 36 weeks. The BRAVE-AA1 and BRAVE-AA2 trials consisted of a total of 1200 patients, with only 98 identifying as Black. Of these 98 patients, 33 were randomly selected to receive placebo.³ With studies now suggesting that Black individuals have greater odds of AA compared with White individuals⁶ and Black patients being more likely to seek medical care for AA,⁷ the BRAVE-AA1 and BRAVE-AA2 study population did not allow for significant comparative data for Black patients. These studies did not document Latino patient involvement.³ Future studies in AA must recruit a diversified group of study participants to better reflect the patients with an increased likelihood of presenting with AA.

Other Treatments on the Horizon

Baricitinib likely will remain alone in its class for only a short time. Phase 3 trials have been completed for ritlecitinib, brepocitinib, and deuruxolitinib for AA. Ritlecitinib, an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, has met all end points in a phase 2b/3 study.¹¹ Brepocitinib is an oral tyrosine kinase 2/JAK1 inhibitor,¹² and deuruxolitinib is an investigational JAK1/2 inhibitor for AA.¹³

Prior authorizations have been the initial step for many drugs in varying fields of medical practice. A study completed in 2016 suggested that insurance coverage for biologics used in the treatment of psoriasis was becoming increasingly difficult.¹⁴ Prior authorization requirement rates increased from 16% of patients in 2009 to 75% in 2014. The decision time also increased from 3.7 days in 2009 to 6.7 days in 2014. The most common reason for delay in decisions and denials was due to step therapy.¹⁴ Insurance companies wanted many patients to try less expensive treatment options prior to “stepping up” to more expensive treatments. Although this may be the case in the treatment of psoriasis, the role of step therapy is unclear for patients with AA because there is only 1 FDA-approved medication. This sets out an ambiguous future for our patients with AA and approval for baricitinib.

The time required for the correspondence between insurance companies, clinic staff, and patients for drug approval may delay treatments, and not all providers have enough staff to coordinate and perform this work. For Black patients, who may present more frequently and with more severe disease,⁷ this could lead to a health care disparity due to the likelihood of the increased need for biologic treatment. Because Black patients have an increased likelihood of being uninsured or underinsured,¹⁵ this further decreases the chances of the most severe AA patients receiving the most helpful medication for their condition.

Many pharmaceutical companies have drug cost assistance programs that aim to provide support covering expensive medications for patients unable to afford them. Although this is a good first step, treatment with any JAK inhibitor potentially can be lifelong. Regarding the social determinants of health, it is known that access to medications does not solely depend on cost. Transportation and access to qualified health professionals are among the issues that create barriers to health care. Instilling long-term practices to ensure equal access to JAK inhibitors and treatment of AA may be the cornerstone to treating AA with equity. Whether we require pharmaceutical companies to make sure all patients have equal access to medications or provide community resources to hairstylists and federally qualified health centers, raising awareness and advocating for and creating attainable access to treatment modalities is imperative to providing well-rounded care to a diverse population.

With the introduction of the first US Food and Drug Administration (FDA)–approved medication for alopecia areata (AA)—the Janus kinase (JAK) inhibitor, baricitinib—there is an important focus on this disease in the literature and for practicing dermatologists. Known by all as an autoimmune genetic disease that causes relapsing and remitting nonscarring hair loss, AA is a condition where the psychological burden has been less widely recognized. Patients with AA have reported lower health-related quality of life scores compared to patients with other skin conditions, including psoriasis or atopic dermatitis. In addition, a lesser amount of scalp coverage is negatively correlated to health-related quality of life scores.¹ Patients with AA also have a 39% lifetime prevalence of major depressive disorder and generalized anxiety disorder.² The treatment of AA has been a hodgepodge of topical, intralesional, and systemic agents, all with indirect immunosuppressive or anagen prolongation effects. Now that there is an approved therapy for AA with more treatments likely to be approved in the near future, there must be a focus on real-world outcomes. With the dawn of a new era in the treatment of AA as well as new information showcasing an altered prevalence of AA in skin of color, highlighting disparities among this population may help ease challenges dermatologic providers will face.

Efficacy of Baricitinib in Different Races and Ethnicities

How will patients of different races and ethnicities respond to this new treatment, and how will their emotional health be affected? The 2 phase 3 pivotal trials showing efficacy of baricitinib in AA included Black and Latino patients but not in a way that is representative of the US population.³ Until recently, the most commonly used prevalence of AA in the United States was from the NHANES I study completed between 1971 and 1974, which was between 0.1% and 0.2%⁴ with minimal focus on race and ethnicity. Recent studies suggest that there may be increased prevalence of this condition in Black patients in the United States. These new findings raise concern around access to care and treatment and the need to tailor psychosocial interventions for populations that may not currently have these supports.

A large cross-sectional study published in 2020 demonstrated that these data remained similar, with a lifetime prevalence of 0.21%.⁵ Of the 45,016 participants—representative of the US population based on the 2015 US Census—the average age of AA patients was 41.2 years, with 61.3% being White and not of Hispanic origin.⁵ In recent years, other studies have challenged the narrative that AA predominantly affects White patients.^6-8 A different cross-sectional study utilizing National Alopecia Areata Registry data from 2002 to 2016 suggested that Black patients have greater odds of developing AA.⁶ In this study of 2645 cases of AA, the odds ratios of developing the condition were 1.36 for Blacks, 0.53 for Asians, and 0.83 for Hispanics compared with the referent White population. These results were consistent through the varying subtypes of AA.⁶ In a reply to these findings, Gonzalez and Fleischer⁷ analyzed data from the 2007 to 2016 National Ambulatory Medical Care Survey database with a focus on racial and ethnic prevalence of AA. This study concluded that Latino and non-White individuals had an increased likelihood of clinician visits for AA compared with White individuals.⁷

More evidence of the Black predominance of AA was demonstrated in a study published in 2018. In this large-scale study, 63,960 women from the Nurses’ Health Study (NHS) and 88,368 women from the Nurses’ Health Study II (NHSII) were included to examine prevalence of disease among these US women.⁸ Analysis showed increased odds of AA based on self-reported race in Black and Hispanic women. Lifetime incidence of AA was greater in Black women, with 2.63 and 5.23 in NHS and NHSII, respectively. It was hypothesized that hairstyling practices in Black and Hispanic women may cause AA to be more noticeable,⁸ which may drive patients to seek medical evaluation.

Feaster and McMichael⁹ published information on the epidemiology of AA in a busy hair loss clinic. This retrospective single-institution study of 265 pediatric and adult Black patients with AA seen over a 5-year period showed that patients aged 18 to 34 years were most likely to present for care, which accounted for 35.8% of the study population, followed by patients aged 10 to 17 years, which accounted for 15.1%. This study also found that females were the larger segment of AA patients, with an increased distribution of disease in young patients. Most of these patients (68.2%) had patchy hair loss, and the ophiasis pattern was seen in 15.1%.⁹ Although the pathogenesis of AA is linked to autoimmunity,¹⁰ the leading cause for these epidemiologic findings of increased prevalence in Black patients is still uncertain.

Baricitinib for AA

In June 2022, the FDA announced the first biologic drug approved for the treatment of AA—baricitinib. Baricitinib is an oral, selective, reversible inhibitor of JAK1 and JAK2.³ The phase 3 trials for baricitinib—BRAVE-AA1 (N=654) and BRAVE-AA2 (N=546)—were conducted between March 2019 and May 2020. In these double-blind, parallel-group, randomized, placebo-controlled trials, 33% of the patient population receiving baricitinib accomplished 80% or more scalp coverage at 36 weeks. The Severity of Alopecia Tool (SALT) score also decreased to 20 or less in 36 weeks. The BRAVE-AA1 and BRAVE-AA2 trials consisted of a total of 1200 patients, with only 98 identifying as Black. Of these 98 patients, 33 were randomly selected to receive placebo.³ With studies now suggesting that Black individuals have greater odds of AA compared with White individuals⁶ and Black patients being more likely to seek medical care for AA,⁷ the BRAVE-AA1 and BRAVE-AA2 study population did not allow for significant comparative data for Black patients. These studies did not document Latino patient involvement.³ Future studies in AA must recruit a diversified group of study participants to better reflect the patients with an increased likelihood of presenting with AA.

Other Treatments on the Horizon

Baricitinib likely will remain alone in its class for only a short time. Phase 3 trials have been completed for ritlecitinib, brepocitinib, and deuruxolitinib for AA. Ritlecitinib, an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, has met all end points in a phase 2b/3 study.¹¹ Brepocitinib is an oral tyrosine kinase 2/JAK1 inhibitor,¹² and deuruxolitinib is an investigational JAK1/2 inhibitor for AA.¹³

Prior authorizations have been the initial step for many drugs in varying fields of medical practice. A study completed in 2016 suggested that insurance coverage for biologics used in the treatment of psoriasis was becoming increasingly difficult.¹⁴ Prior authorization requirement rates increased from 16% of patients in 2009 to 75% in 2014. The decision time also increased from 3.7 days in 2009 to 6.7 days in 2014. The most common reason for delay in decisions and denials was due to step therapy.¹⁴ Insurance companies wanted many patients to try less expensive treatment options prior to “stepping up” to more expensive treatments. Although this may be the case in the treatment of psoriasis, the role of step therapy is unclear for patients with AA because there is only 1 FDA-approved medication. This sets out an ambiguous future for our patients with AA and approval for baricitinib.

The time required for the correspondence between insurance companies, clinic staff, and patients for drug approval may delay treatments, and not all providers have enough staff to coordinate and perform this work. For Black patients, who may present more frequently and with more severe disease,⁷ this could lead to a health care disparity due to the likelihood of the increased need for biologic treatment. Because Black patients have an increased likelihood of being uninsured or underinsured,¹⁵ this further decreases the chances of the most severe AA patients receiving the most helpful medication for their condition.

Many pharmaceutical companies have drug cost assistance programs that aim to provide support covering expensive medications for patients unable to afford them. Although this is a good first step, treatment with any JAK inhibitor potentially can be lifelong. Regarding the social determinants of health, it is known that access to medications does not solely depend on cost. Transportation and access to qualified health professionals are among the issues that create barriers to health care. Instilling long-term practices to ensure equal access to JAK inhibitors and treatment of AA may be the cornerstone to treating AA with equity. Whether we require pharmaceutical companies to make sure all patients have equal access to medications or provide community resources to hairstylists and federally qualified health centers, raising awareness and advocating for and creating attainable access to treatment modalities is imperative to providing well-rounded care to a diverse population.

With the introduction of the first US Food and Drug Administration (FDA)–approved medication for alopecia areata (AA)—the Janus kinase (JAK) inhibitor, baricitinib—there is an important focus on this disease in the literature and for practicing dermatologists. Known by all as an autoimmune genetic disease that causes relapsing and remitting nonscarring hair loss, AA is a condition where the psychological burden has been less widely recognized. Patients with AA have reported lower health-related quality of life scores compared to patients with other skin conditions, including psoriasis or atopic dermatitis. In addition, a lesser amount of scalp coverage is negatively correlated to health-related quality of life scores.¹ Patients with AA also have a 39% lifetime prevalence of major depressive disorder and generalized anxiety disorder.² The treatment of AA has been a hodgepodge of topical, intralesional, and systemic agents, all with indirect immunosuppressive or anagen prolongation effects. Now that there is an approved therapy for AA with more treatments likely to be approved in the near future, there must be a focus on real-world outcomes. With the dawn of a new era in the treatment of AA as well as new information showcasing an altered prevalence of AA in skin of color, highlighting disparities among this population may help ease challenges dermatologic providers will face.

Efficacy of Baricitinib in Different Races and Ethnicities

How will patients of different races and ethnicities respond to this new treatment, and how will their emotional health be affected? The 2 phase 3 pivotal trials showing efficacy of baricitinib in AA included Black and Latino patients but not in a way that is representative of the US population.³ Until recently, the most commonly used prevalence of AA in the United States was from the NHANES I study completed between 1971 and 1974, which was between 0.1% and 0.2%⁴ with minimal focus on race and ethnicity. Recent studies suggest that there may be increased prevalence of this condition in Black patients in the United States. These new findings raise concern around access to care and treatment and the need to tailor psychosocial interventions for populations that may not currently have these supports.

A large cross-sectional study published in 2020 demonstrated that these data remained similar, with a lifetime prevalence of 0.21%.⁵ Of the 45,016 participants—representative of the US population based on the 2015 US Census—the average age of AA patients was 41.2 years, with 61.3% being White and not of Hispanic origin.⁵ In recent years, other studies have challenged the narrative that AA predominantly affects White patients.^6-8 A different cross-sectional study utilizing National Alopecia Areata Registry data from 2002 to 2016 suggested that Black patients have greater odds of developing AA.⁶ In this study of 2645 cases of AA, the odds ratios of developing the condition were 1.36 for Blacks, 0.53 for Asians, and 0.83 for Hispanics compared with the referent White population. These results were consistent through the varying subtypes of AA.⁶ In a reply to these findings, Gonzalez and Fleischer⁷ analyzed data from the 2007 to 2016 National Ambulatory Medical Care Survey database with a focus on racial and ethnic prevalence of AA. This study concluded that Latino and non-White individuals had an increased likelihood of clinician visits for AA compared with White individuals.⁷

More evidence of the Black predominance of AA was demonstrated in a study published in 2018. In this large-scale study, 63,960 women from the Nurses’ Health Study (NHS) and 88,368 women from the Nurses’ Health Study II (NHSII) were included to examine prevalence of disease among these US women.⁸ Analysis showed increased odds of AA based on self-reported race in Black and Hispanic women. Lifetime incidence of AA was greater in Black women, with 2.63 and 5.23 in NHS and NHSII, respectively. It was hypothesized that hairstyling practices in Black and Hispanic women may cause AA to be more noticeable,⁸ which may drive patients to seek medical evaluation.

Feaster and McMichael⁹ published information on the epidemiology of AA in a busy hair loss clinic. This retrospective single-institution study of 265 pediatric and adult Black patients with AA seen over a 5-year period showed that patients aged 18 to 34 years were most likely to present for care, which accounted for 35.8% of the study population, followed by patients aged 10 to 17 years, which accounted for 15.1%. This study also found that females were the larger segment of AA patients, with an increased distribution of disease in young patients. Most of these patients (68.2%) had patchy hair loss, and the ophiasis pattern was seen in 15.1%.⁹ Although the pathogenesis of AA is linked to autoimmunity,¹⁰ the leading cause for these epidemiologic findings of increased prevalence in Black patients is still uncertain.

Baricitinib for AA

In June 2022, the FDA announced the first biologic drug approved for the treatment of AA—baricitinib. Baricitinib is an oral, selective, reversible inhibitor of JAK1 and JAK2.³ The phase 3 trials for baricitinib—BRAVE-AA1 (N=654) and BRAVE-AA2 (N=546)—were conducted between March 2019 and May 2020. In these double-blind, parallel-group, randomized, placebo-controlled trials, 33% of the patient population receiving baricitinib accomplished 80% or more scalp coverage at 36 weeks. The Severity of Alopecia Tool (SALT) score also decreased to 20 or less in 36 weeks. The BRAVE-AA1 and BRAVE-AA2 trials consisted of a total of 1200 patients, with only 98 identifying as Black. Of these 98 patients, 33 were randomly selected to receive placebo.³ With studies now suggesting that Black individuals have greater odds of AA compared with White individuals⁶ and Black patients being more likely to seek medical care for AA,⁷ the BRAVE-AA1 and BRAVE-AA2 study population did not allow for significant comparative data for Black patients. These studies did not document Latino patient involvement.³ Future studies in AA must recruit a diversified group of study participants to better reflect the patients with an increased likelihood of presenting with AA.

Other Treatments on the Horizon

Baricitinib likely will remain alone in its class for only a short time. Phase 3 trials have been completed for ritlecitinib, brepocitinib, and deuruxolitinib for AA. Ritlecitinib, an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, has met all end points in a phase 2b/3 study.¹¹ Brepocitinib is an oral tyrosine kinase 2/JAK1 inhibitor,¹² and deuruxolitinib is an investigational JAK1/2 inhibitor for AA.¹³

Prior authorizations have been the initial step for many drugs in varying fields of medical practice. A study completed in 2016 suggested that insurance coverage for biologics used in the treatment of psoriasis was becoming increasingly difficult.¹⁴ Prior authorization requirement rates increased from 16% of patients in 2009 to 75% in 2014. The decision time also increased from 3.7 days in 2009 to 6.7 days in 2014. The most common reason for delay in decisions and denials was due to step therapy.¹⁴ Insurance companies wanted many patients to try less expensive treatment options prior to “stepping up” to more expensive treatments. Although this may be the case in the treatment of psoriasis, the role of step therapy is unclear for patients with AA because there is only 1 FDA-approved medication. This sets out an ambiguous future for our patients with AA and approval for baricitinib.

The time required for the correspondence between insurance companies, clinic staff, and patients for drug approval may delay treatments, and not all providers have enough staff to coordinate and perform this work. For Black patients, who may present more frequently and with more severe disease,⁷ this could lead to a health care disparity due to the likelihood of the increased need for biologic treatment. Because Black patients have an increased likelihood of being uninsured or underinsured,¹⁵ this further decreases the chances of the most severe AA patients receiving the most helpful medication for their condition.

Many pharmaceutical companies have drug cost assistance programs that aim to provide support covering expensive medications for patients unable to afford them. Although this is a good first step, treatment with any JAK inhibitor potentially can be lifelong. Regarding the social determinants of health, it is known that access to medications does not solely depend on cost. Transportation and access to qualified health professionals are among the issues that create barriers to health care. Instilling long-term practices to ensure equal access to JAK inhibitors and treatment of AA may be the cornerstone to treating AA with equity. Whether we require pharmaceutical companies to make sure all patients have equal access to medications or provide community resources to hairstylists and federally qualified health centers, raising awareness and advocating for and creating attainable access to treatment modalities is imperative to providing well-rounded care to a diverse population.

Practice Gap

Cutaneous surgery involves many areas where skin is quite thin and fragile, which often is encountered in elderly patients; the forearms and lower legs are the most frequent locations for thin skin.¹ Dermatologic surgeons frequently encounter these situations, making this a highly practical arena for technical improvements.

For many of these patients, there is little meaningful dermis for placement of subcutaneous sutures. Therefore, a common approach following surgery, particularly following Mohs micrographic surgery in which tumors and defects typically are larger, is healing by secondary intention.² Although healing by secondary intention often is a reasonable option, we have found that maximizing the use of epidermal skin for primary closure can be an effective means of closing many such defects. Antimicrobial reinforced skin closure strips have been incorporated in wound closure for thin skin. However, earlier efforts involving reinforcement perpendicular to the wound lacked critical details or used a different technique.³

The Technique

We developed a novel effective closure technique that minimizes these problems. Our technique has been used on the wounds of hundreds of patients with satisfying results. Early on, we used multiple variations to optimize outcomes, including different sizes of sutures and reinforced skin closure strips, application of medical liquid adhesive, liquid adhesive, and varying postoperative dressings. For 3 years, we tracked outcomes in-house and gradually narrowed down our successes into a single, user-friendly paradigm.

Supplies—To perform this technique, required supplies include:

• 2-0 Polypropylene suture with a PS-2 needle, or the equivalent. Polyglactin or silk suture can be utilized if a less-rigid suture is desired; however, we primarily have used polypropylene for repairs with good results. Each repair requires at least 2 sutures.

• Reinforced skin closure strips (1×5 inches). This width affords increased strength.

• Conforming stretch bandage and elastic self-adherent wrap.

• Polysporin (bacitracin zinc, polymyxin B sulfate, and petrolatum)(Johnson & Johnson).

• All usual surgical instruments and supplies, including paper tape and nonadherent gauze (surgeon dependent).

Step-by-step Technique—Close the wound using the following steps:

1. Once the defect is finalized following Mohs micrographic surgery or excision, excise the ellipse to be utilized for the closure and perform complete hemostasis.

2. Place 2 layers of reinforced skin closure strips—one on top of the other—along each side of the defect, leaving approximately 1 cm of uncovered skin between the wound edges and the reinforced skin closure strips (Figure, A).

3. Take a big-bite pulley suture about one-third of the way from one end of the ellipse, with both punctures passing through the reinforced skin closure strips. Leave that in place or have the assistant hold it and wait. Place a second suture immediately adjacent to the pulley suture. Once that suture is placed but still untied, have the assistant carefully pull the pulley suture outward away from the wound edge while you carefully bring the suture together and tie it off gently (Figure, B). Doing this utilizes the pulley ability of the suture to protect the skin from tearing and releases sufficient pressure on the single suture so that it can be easily tightened without risk to the fragile skin.

4. Repeat step 3, this time placing a pulley suture near the midline of the ellipse and the subsequent single suture adjacent to it.

5. Take pulley sutures repeatedly as in steps 3 and 4 until multiple sutures are secured in place. Replace the pulley sutures with single sutures because the double-pulley sutures in areas of lower vascularity tend to have, in our experience, a slightly increased incidence of focal necrosis in comparison to single sutures.

6. Make a concerted attempt to keep as much blood as possible off the reinforced skin closure strips throughout the procedure; the less dried blood on the reinforced skin closure strips, the cleaner and better the final closure (Figure, C).

7. Most of these cases involve the forearms and the legs below the knees. Because any increase in pressure or swelling on the wound can result in skin breakdown, postoperative dressing is critical. We use a layered approach; the following sequence can be modified to the preference of the surgeon: Polysporin (bacitracin zinc, polymyxin B sulfate, and petrolatum), nonadherent gauze, paper tape, conforming stretch bandage, and elastic self-adherent wrap. Minimizing swelling and infection are the primary goals. The wrap is left on for 1 week and should be kept dry.

8. Have the patient return to the office in 1 week. Unwrap the entire wound; trim back the reinforced skin closure strips; and have the patient utilize typical wound care at home thereafter consisting of cleaning and application of Polysporin or plain petrolatum, nonadherent gauze, and a paper-tape bandage. Because liquid adhesive is not utilized in this technique, the reinforced skin closure strips can be carefully removed without tearing skin. Leave sutures in for 3 weeks for arm procedures and 4 weeks for leg procedures, unless irritation develops or rapid suture overgrowth occurs in either location.

Complications

Most outcomes after using this technique are typical of optimized linear surgeries, with reduced scarring and complete wound healing (Figure, D). We seldom see complications but the following are possible:

• Bleeding occurs but rarely; the weeklong wrap likely provides great benefit.

• Infection is rare but does occur occasionally, as in any surgical procedure.

• Breakdown of the entire wound is rare; however, we occasionally see focal necrosis near 1 stitch—or rarely 2 stitches—that does not require intervention, apart from longer use of topical Polysporin or petrolatum alone to maximize healing by secondary intention in those small areas.• Despite simple suture placement far from the edge of the wound, wound inversion is seldom a problem because these taut closures have a tendency to expand slightly due to postoperative swelling.

Practice Implications

Any experienced dermatologic surgeon can perfect this technique for closing a wound in thin skin. Because wound closure in areas of fragile skin frequently is encountered in cutaneous surgery, we hope that utilizing this technique results in an optimal outcome for many patients.

Practice Gap

Cutaneous surgery involves many areas where skin is quite thin and fragile, which often is encountered in elderly patients; the forearms and lower legs are the most frequent locations for thin skin.¹ Dermatologic surgeons frequently encounter these situations, making this a highly practical arena for technical improvements.

For many of these patients, there is little meaningful dermis for placement of subcutaneous sutures. Therefore, a common approach following surgery, particularly following Mohs micrographic surgery in which tumors and defects typically are larger, is healing by secondary intention.² Although healing by secondary intention often is a reasonable option, we have found that maximizing the use of epidermal skin for primary closure can be an effective means of closing many such defects. Antimicrobial reinforced skin closure strips have been incorporated in wound closure for thin skin. However, earlier efforts involving reinforcement perpendicular to the wound lacked critical details or used a different technique.³

The Technique

We developed a novel effective closure technique that minimizes these problems. Our technique has been used on the wounds of hundreds of patients with satisfying results. Early on, we used multiple variations to optimize outcomes, including different sizes of sutures and reinforced skin closure strips, application of medical liquid adhesive, liquid adhesive, and varying postoperative dressings. For 3 years, we tracked outcomes in-house and gradually narrowed down our successes into a single, user-friendly paradigm.

Supplies—To perform this technique, required supplies include:

• 2-0 Polypropylene suture with a PS-2 needle, or the equivalent. Polyglactin or silk suture can be utilized if a less-rigid suture is desired; however, we primarily have used polypropylene for repairs with good results. Each repair requires at least 2 sutures.

• Reinforced skin closure strips (1×5 inches). This width affords increased strength.

• Conforming stretch bandage and elastic self-adherent wrap.

• Polysporin (bacitracin zinc, polymyxin B sulfate, and petrolatum)(Johnson & Johnson).

• All usual surgical instruments and supplies, including paper tape and nonadherent gauze (surgeon dependent).

Step-by-step Technique—Close the wound using the following steps:

1. Once the defect is finalized following Mohs micrographic surgery or excision, excise the ellipse to be utilized for the closure and perform complete hemostasis.

2. Place 2 layers of reinforced skin closure strips—one on top of the other—along each side of the defect, leaving approximately 1 cm of uncovered skin between the wound edges and the reinforced skin closure strips (Figure, A).

3. Take a big-bite pulley suture about one-third of the way from one end of the ellipse, with both punctures passing through the reinforced skin closure strips. Leave that in place or have the assistant hold it and wait. Place a second suture immediately adjacent to the pulley suture. Once that suture is placed but still untied, have the assistant carefully pull the pulley suture outward away from the wound edge while you carefully bring the suture together and tie it off gently (Figure, B). Doing this utilizes the pulley ability of the suture to protect the skin from tearing and releases sufficient pressure on the single suture so that it can be easily tightened without risk to the fragile skin.

4. Repeat step 3, this time placing a pulley suture near the midline of the ellipse and the subsequent single suture adjacent to it.

5. Take pulley sutures repeatedly as in steps 3 and 4 until multiple sutures are secured in place. Replace the pulley sutures with single sutures because the double-pulley sutures in areas of lower vascularity tend to have, in our experience, a slightly increased incidence of focal necrosis in comparison to single sutures.

6. Make a concerted attempt to keep as much blood as possible off the reinforced skin closure strips throughout the procedure; the less dried blood on the reinforced skin closure strips, the cleaner and better the final closure (Figure, C).

7. Most of these cases involve the forearms and the legs below the knees. Because any increase in pressure or swelling on the wound can result in skin breakdown, postoperative dressing is critical. We use a layered approach; the following sequence can be modified to the preference of the surgeon: Polysporin (bacitracin zinc, polymyxin B sulfate, and petrolatum), nonadherent gauze, paper tape, conforming stretch bandage, and elastic self-adherent wrap. Minimizing swelling and infection are the primary goals. The wrap is left on for 1 week and should be kept dry.

8. Have the patient return to the office in 1 week. Unwrap the entire wound; trim back the reinforced skin closure strips; and have the patient utilize typical wound care at home thereafter consisting of cleaning and application of Polysporin or plain petrolatum, nonadherent gauze, and a paper-tape bandage. Because liquid adhesive is not utilized in this technique, the reinforced skin closure strips can be carefully removed without tearing skin. Leave sutures in for 3 weeks for arm procedures and 4 weeks for leg procedures, unless irritation develops or rapid suture overgrowth occurs in either location.

Complications

Most outcomes after using this technique are typical of optimized linear surgeries, with reduced scarring and complete wound healing (Figure, D). We seldom see complications but the following are possible:

• Bleeding occurs but rarely; the weeklong wrap likely provides great benefit.

• Infection is rare but does occur occasionally, as in any surgical procedure.

• Breakdown of the entire wound is rare; however, we occasionally see focal necrosis near 1 stitch—or rarely 2 stitches—that does not require intervention, apart from longer use of topical Polysporin or petrolatum alone to maximize healing by secondary intention in those small areas.• Despite simple suture placement far from the edge of the wound, wound inversion is seldom a problem because these taut closures have a tendency to expand slightly due to postoperative swelling.

Practice Implications

Any experienced dermatologic surgeon can perfect this technique for closing a wound in thin skin. Because wound closure in areas of fragile skin frequently is encountered in cutaneous surgery, we hope that utilizing this technique results in an optimal outcome for many patients.

Practice Gap

Cutaneous surgery involves many areas where skin is quite thin and fragile, which often is encountered in elderly patients; the forearms and lower legs are the most frequent locations for thin skin.¹ Dermatologic surgeons frequently encounter these situations, making this a highly practical arena for technical improvements.

For many of these patients, there is little meaningful dermis for placement of subcutaneous sutures. Therefore, a common approach following surgery, particularly following Mohs micrographic surgery in which tumors and defects typically are larger, is healing by secondary intention.² Although healing by secondary intention often is a reasonable option, we have found that maximizing the use of epidermal skin for primary closure can be an effective means of closing many such defects. Antimicrobial reinforced skin closure strips have been incorporated in wound closure for thin skin. However, earlier efforts involving reinforcement perpendicular to the wound lacked critical details or used a different technique.³

The Technique

We developed a novel effective closure technique that minimizes these problems. Our technique has been used on the wounds of hundreds of patients with satisfying results. Early on, we used multiple variations to optimize outcomes, including different sizes of sutures and reinforced skin closure strips, application of medical liquid adhesive, liquid adhesive, and varying postoperative dressings. For 3 years, we tracked outcomes in-house and gradually narrowed down our successes into a single, user-friendly paradigm.

Supplies—To perform this technique, required supplies include:

• 2-0 Polypropylene suture with a PS-2 needle, or the equivalent. Polyglactin or silk suture can be utilized if a less-rigid suture is desired; however, we primarily have used polypropylene for repairs with good results. Each repair requires at least 2 sutures.

• Reinforced skin closure strips (1×5 inches). This width affords increased strength.

• Conforming stretch bandage and elastic self-adherent wrap.

• Polysporin (bacitracin zinc, polymyxin B sulfate, and petrolatum)(Johnson & Johnson).

• All usual surgical instruments and supplies, including paper tape and nonadherent gauze (surgeon dependent).

Step-by-step Technique—Close the wound using the following steps:

1. Once the defect is finalized following Mohs micrographic surgery or excision, excise the ellipse to be utilized for the closure and perform complete hemostasis.

2. Place 2 layers of reinforced skin closure strips—one on top of the other—along each side of the defect, leaving approximately 1 cm of uncovered skin between the wound edges and the reinforced skin closure strips (Figure, A).

3. Take a big-bite pulley suture about one-third of the way from one end of the ellipse, with both punctures passing through the reinforced skin closure strips. Leave that in place or have the assistant hold it and wait. Place a second suture immediately adjacent to the pulley suture. Once that suture is placed but still untied, have the assistant carefully pull the pulley suture outward away from the wound edge while you carefully bring the suture together and tie it off gently (Figure, B). Doing this utilizes the pulley ability of the suture to protect the skin from tearing and releases sufficient pressure on the single suture so that it can be easily tightened without risk to the fragile skin.

4. Repeat step 3, this time placing a pulley suture near the midline of the ellipse and the subsequent single suture adjacent to it.

5. Take pulley sutures repeatedly as in steps 3 and 4 until multiple sutures are secured in place. Replace the pulley sutures with single sutures because the double-pulley sutures in areas of lower vascularity tend to have, in our experience, a slightly increased incidence of focal necrosis in comparison to single sutures.

6. Make a concerted attempt to keep as much blood as possible off the reinforced skin closure strips throughout the procedure; the less dried blood on the reinforced skin closure strips, the cleaner and better the final closure (Figure, C).

7. Most of these cases involve the forearms and the legs below the knees. Because any increase in pressure or swelling on the wound can result in skin breakdown, postoperative dressing is critical. We use a layered approach; the following sequence can be modified to the preference of the surgeon: Polysporin (bacitracin zinc, polymyxin B sulfate, and petrolatum), nonadherent gauze, paper tape, conforming stretch bandage, and elastic self-adherent wrap. Minimizing swelling and infection are the primary goals. The wrap is left on for 1 week and should be kept dry.

8. Have the patient return to the office in 1 week. Unwrap the entire wound; trim back the reinforced skin closure strips; and have the patient utilize typical wound care at home thereafter consisting of cleaning and application of Polysporin or plain petrolatum, nonadherent gauze, and a paper-tape bandage. Because liquid adhesive is not utilized in this technique, the reinforced skin closure strips can be carefully removed without tearing skin. Leave sutures in for 3 weeks for arm procedures and 4 weeks for leg procedures, unless irritation develops or rapid suture overgrowth occurs in either location.

Complications

Most outcomes after using this technique are typical of optimized linear surgeries, with reduced scarring and complete wound healing (Figure, D). We seldom see complications but the following are possible:

• Bleeding occurs but rarely; the weeklong wrap likely provides great benefit.

• Infection is rare but does occur occasionally, as in any surgical procedure.

• Breakdown of the entire wound is rare; however, we occasionally see focal necrosis near 1 stitch—or rarely 2 stitches—that does not require intervention, apart from longer use of topical Polysporin or petrolatum alone to maximize healing by secondary intention in those small areas.• Despite simple suture placement far from the edge of the wound, wound inversion is seldom a problem because these taut closures have a tendency to expand slightly due to postoperative swelling.

Practice Implications

Any experienced dermatologic surgeon can perfect this technique for closing a wound in thin skin. Because wound closure in areas of fragile skin frequently is encountered in cutaneous surgery, we hope that utilizing this technique results in an optimal outcome for many patients.

LAS VEGAS – Vitiligo affects individuals of all ages, and “the social impact is huge,” David Rosmarin, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.

SolStock/Moment/Getty Images

Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.

The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.

Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.

In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.

Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.

In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.

In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.

Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.

Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.

JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.

Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.

An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.

Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.

Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.

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

LAS VEGAS – Vitiligo affects individuals of all ages, and “the social impact is huge,” David Rosmarin, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.

SolStock/Moment/Getty Images

Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.

The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.

Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.

In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.

Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.

In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.

In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.

Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.

Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.

JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.

Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.

An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.

Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.

Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.

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

LAS VEGAS – Vitiligo affects individuals of all ages, and “the social impact is huge,” David Rosmarin, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Vitiligo, an autoimmune condition that results in patches of skin depigmentation, occurs in 0.5% to 2% of the population. The average age of onset is 20 years, with 25% of cases occurring before age 10, and 70%-80% of cases by age 30 years, which means a long-term effect on quality of life, especially for younger patients, said Dr. Rosmarin, vice chair of education and research and director of the clinical trials unit at Tufts University, Boston.

SolStock/Moment/Getty Images

Studies have shown that 95% of 15- to 17-year-olds with vitiligo are bothered by it, as are approximately 50% of children aged 6-14 years, he said. Although patients with more extensive lesions on the face, arms, legs, and hands report worse quality of life, they report that uncontrolled progression of vitiligo is more concerning than the presence of lesions in exposed areas, he noted.

The current strategy for getting vitiligo under control is a two-step process, said Dr. Rosmarin. First, improve the skin environment by suppressing the overactive immune system, then encourage repigmentation and “nudge the melanocytes to return,” he said.

Topical ruxolitinib, a Janus kinase (JAK) inhibitor, is the latest tool for dermatologists to help give the melanocytes that nudge. In July 2022, the Food and Drug Administration approved ruxolitinib cream for treating nonsegmental vitiligo in patients 12 years of age and older – the first treatment approved to repigment patients with vitiligo.

Vitiligo is driven in part by interferon (IFN)-gamma signaling through JAK 1 and 2, and ruxolitinib acts as an inhibitor, Dr. Rosmarin said.

In the TRuE-V1 and TRuE-V2 studies presented at the 2022 European Academy of Dermatology and Venereology meeting in Milan, adolescents and adults with vitiligo who were randomized to 1.5% ruxolitinib cream twice daily showed significant improvement over those randomized to the vehicle by 24 weeks, at which time all patients could continue with ruxolitinib through 52 weeks, he said.

Dr. Rosmarin presented 52-week data from the TRuE-V1 and TRuE-V2 studies at the 2022 American Academy of Dermatology meeting in Boston. He was the lead author of the studies that were subsequently published in the New England Journal of Medicine.

In the two studies, 52.6% and 48% of the patients in the ruxolitinib groups achieved the primary outcome of at least 75% improvement on the Facial Vitiligo Area Scoring Index (F-VASI75) by 52 weeks, compared with 26.8% and 29.6% of patients on the vehicle, respectively.

In addition, at 52 weeks, 53.2% and 49.2% of patients treated with ruxolitinib in the two studies achieved 50% improvement on the Total Vitiligo Area Scoring Index (T-VASI50), a clinician assessment of affected body surface area and level of depigmentation, compared with 31.7% and 22.2% of those on vehicle, respectively.

Patient satisfaction was high with ruxolitinib, Dr. Rosmarin said. In the TRuE-V1 and TRuE-V2 studies, 39.9% and 32.8% of patients, respectively, achieved a successful treatment response based on the patient-reported Vitiligo Noticeability Scale (VNS) by week 52, versus 19.5% and 13.6% of those on vehicle.

Ruxolitinib cream was well tolerated, with “no clinically significant application site reactions or serious treatment-related adverse events,” he noted. The most common treatment-related adverse events across the TRuE-V1 and TRuE-V2 studies were acne at the application site (affecting about 6% of patients) and pruritus at the application site about (affecting 5%), said Dr. Rosmarin.

JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, have shown effectiveness for vitiligo, which supports the potential role of the IFN-gamma-chemokine signaling axis in the pathogenesis of the disease, said Dr. Rosmarin. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition.

Ruxolitinib’s success has been consistent across subgroups of age, gender, race, geographic region, and Fitzpatrick skin phototype. Notably, ruxolitinib was effective among the adolescent population, with approximately 60% achieving T-VASI50 and success based on VNS in TRuE-V1 and TRuE-V2.

An oral version of ruxolitinib is in clinical trials, which “makes a lot of sense,” Dr. Rosmarin said. “Patients don’t always have localized disease,” and such patients may benefit from an oral therapy. Topicals may have the advantage in terms of safety, but questions of maintenance remain, he said. Oral treatments may be useful for patients with large body surface areas affected, and those with unstable or progressive disease, he added.

Areas for additional research include combination therapy with ruxolitinib and phototherapy, and an anti-IL 15 therapy in the pipeline has the potential to drive vitiligo into remission, Dr. Rosmarin said. In a study known as REVEAL that is still recruiting patients, researchers will test the efficacy of an IL-15 inhibitor known as AMG 714 to induce facial repigmentation in adults with vitiligo.

Dr. Rosmarin disclosed ties with AbbVie, Abcuro, AltruBio, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb Company, Celgene, Concert Pharmaceuticals, CSL Behring, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Kirin, Merck, Novartis, Pfizer, Regeneron, Revolo, Sanofi, Sun, UCB, and Viela Bio.

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

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among patients with metastatic melanoma who undergo treatment with single or combination immune checkpoint inhibitors (ICIs) and who experience immune adverse events, overall survival is significantly longer, regardless of the need for hospitalization. Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.

“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.

The study was published online in JAMA Network Open.

Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.

The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.

To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.

Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.

A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.

Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).

In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).

There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).

For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).

The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).

There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.

The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).

“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”

“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.  

Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.

“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.

After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.

Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.

Dr. Watson has received personal fees from Apobiologix Canada.

A version of this article first appeared on Medscape.com.

Among patients with metastatic melanoma who undergo treatment with single or combination immune checkpoint inhibitors (ICIs) and who experience immune adverse events, overall survival is significantly longer, regardless of the need for hospitalization. Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.

“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.

The study was published online in JAMA Network Open.

Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.

The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.

To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.

Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.

A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.

Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).

In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).

There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).

For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).

The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).

There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.

The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).

“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”

“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.  

Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.

“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.

After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.

Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.

Dr. Watson has received personal fees from Apobiologix Canada.

A version of this article first appeared on Medscape.com.

Among patients with metastatic melanoma who undergo treatment with single or combination immune checkpoint inhibitors (ICIs) and who experience immune adverse events, overall survival is significantly longer, regardless of the need for hospitalization. Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.

“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.

The study was published online in JAMA Network Open.

Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.

The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.

To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.

Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.

A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.

Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).

In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).

There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).

For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).

The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).

There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.

The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).

“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”

“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.  

Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.

“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.

After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.

Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.

Dr. Watson has received personal fees from Apobiologix Canada.

A version of this article first appeared on Medscape.com.

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

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

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

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

LAS VEGAS – Although the range of oral psoriasis therapies continues to expand, “topical therapy is still the cornerstone of the treatment of psoriasis,” said Linda Stein Gold, MD, in a presentation at Medscape Live’s annual Las Vegas Dermatology Seminar.

However, when using topical treatments, combination therapy is generally more effective than monotherapy for psoriasis, especially for plaque psoriasis, said Dr. Stein Gold, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit.

petekarici/Getty Images

Two combination products, calcipotriene/betamethasone (CAL/BDP) and tazarotene/halobetasol lotion, each offer a complimentary mechanism of action that minimizes side effects, with decreased irritation and less atrophy, she said. Calcipotriene/betamethasone (CAL/BDP) is available as a cream or foam, Dr. Stein Gold noted. The cream is engineered for rapid onset, as well as enhanced penetration, she said. CAL/BDP foam also is designed for enhanced penetration, and has been shown to have long-term maintenance efficacy, she said.

The currently available CAL/BDP cream is made using a patented technology known as “PAD,” in which the internal oil of the cream vehicle is stabilized by encapsulation in “a robust aqueous film,” Dr. Stein Gold said, noting that the greater solubility enhances skin penetration. The creation of “a robust oil droplet” addresses the problems associated with the surfactants present in many cream vehicles, namely irritation and impedance of skin penetration of the cream, she said.

In an 8-week study published in 2021, researchers compared CAL/BDP cream with PAD technology to CAL/BDP topical suspension in adults with mild to moderate psoriasis.

Patients randomized to treatment with CAL/BDP cream were significantly more likely to achieve the primary endpoint of Physician Global Assessment (PGA) treatment success than those randomized to the topical solution or vehicle (37.4%, 22.8%, and 3.7%, respectively).
 

Get proactive to maintain results

With topical psoriasis treatment, a proactive strategy helps maintain results over time, Dr. Stein Gold said. As an example, she cited a study published in 2021. In that study, known as PSO-LONG, which evaluated topical CAL/BDP foam, proactive management with the CAL/BDP foam formulation, “reduced the risk of experiencing relapse by 43%,” compared with reactive management (treatment with the vehicle foam), she said. Patients in the proactive-management group experienced an average of 41 more days in remission, compared with those in the reactive management group over a 1-year period.

Dr. Stein Gold also highlighted the value of tazarotene/halobetasol lotion for psoriasis, which she described as having synergistic efficacy,

She shared data presented at the 2021 Maui Dermatology meeting showing treatment success by 8 weeks with halobetasol/tazarotene with significantly reduced mean scores on measures of itching, dryness, and burning/stinging, compared with those on vehicle.

What’s new and approved

Joining the current topical treatment options for psoriasis is tapinarof, a small molecule that works by down-regulating Th17 cytokines, said Dr. Stein Gold. Tapinarof is Food and Drug Administration approved for treating psoriasis and is being studied in clinical trials for atopic dermatitis, she noted.

Dr. Stein Gold reviewed data from the PSOARING program published in the New England Journal of Medicine that served as a foundation for the FDA approval of tapinarof 1% cream. In the PSOARING 1 and 2 studies, patients with PSORIASIS showed significant improvement compared with vehicle over 12 weeks for the primary endpoint of Physicians’ Global Assessment scores of 0 or 1 (clear or almost clear). In the two studies, 60.7% and 56.9% of patients randomized to tapinarof met the patient-reported outcome of a minimum 4-point improvement in peak pruritus on the numerical rating scale (NRS) from baseline vs. 43.2% and 29.7% of placebo patients in the two studies, respectively.

In PSOARING 1 and 2, folliculitis (mostly mild or moderate), contact dermatitis, headache, pruritus, and dermatitis were the most common treatment-emergent adverse events, occurring in 1% or more of patients. Adverse event profiles for tapinarof are similar to those seen in previous studies, and a long-term extension showed a consistent safety profile, Dr. Stein Gold said.

Another recently approved topical treatment for psoriasis, a cream formulation of roflumilast, a phosphodiesterase (PDE)-4 inhibitor, has shown efficacy for treating plaque psoriasis, she said.

Patients with psoriasis in the DERMIS 1 and DERMIS 2 phase 3 studies randomized to 0.3% roflumilast cream showed significant improvement compared with those randomized to vehicle in terms of Investigator Global Assessment scores of clear or almost clear with an improvement of at least 2 grades from baseline.

Roflumilast foam also has shown success in improving scalp and body psoriasis, but this vehicle and indication has not yet been approved, Dr. Stein Gold said.

Dr. Stein Gold disclosed serving as a consultant or adviser for companies including AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, EPI Health, Galderma, Janssen, Incyte, Ortho Dermatologics, Pfizer, Regeneron, Sanofi; UCB, and serving as a speaker or member of speakers’ bureau for Amgen, AbbVie, Incyte, Pfizer, Regeneron, Sanofi, and Sun Research. She also disclosed receiving funding from AbbVie Amgen, Arcutis, Dermata, Dermavant, Galderma, Incyte, Ortho Dermatologics, Pfizer, and UCB.

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

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

SAN DIEGO – In the clinical experience of Jeremy B. Green, MD, men typically require a higher dose of facial neuromodulators for nonsurgical wrinkle reduction compared with women because of anatomical differences.

“Men generally have larger facial muscle mass,” Dr. Green, a dermatologist in Coral Gables, Fla., said at the annual Masters of Aesthetics Symposium. “We need a higher dose to treat them, or they will not be happy. In general, I try to increase the dose by about 50% for my male patients.”

Two early trials of dose adjustments support this practice, he said. In one, 80 men were randomized to receive a total dose of either 20, 40, 60, or 80 U of botulinum toxin type A (Botox) in the glabellar area. The researchers found that the 40, 60, and 80 U doses of botulinum toxin type A were consistently more effective in reducing glabellar lines than the 20 U dose.

In a subsequent study, researchers administered botulinum toxin type A (Dysport) 0.5 to 0.7 mL for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation at several time points up to 150 days post treatment. The median duration of effect was 109 days vs. 0 days for placebo in the blinded evaluator evaluation and 107 days vs. 0 for placebo in the patient self-evaluation.

Most injection algorithms for treating the glabella rely on a 5- or 7-point injection technique, but in 2021, researchers led by Sebastian Cotofana, MD, PhD, of the department of clinical anatomy at Mayo Clinic, Rochester, Minn., reported results from a study of the efficacy and safety of a refined 3-point injection technique targeting horizontal and vertical lines to prevent brow ptosis.

“Prior to this study Sebastian asked me, ‘Why do you guys always inject the body of the muscle?’ ” Dr. Green said. “‘If you inject the origin of the muscle on bone, you could more effectively wipe out the entire muscle’s movement. You’re going to get a better result at a lower dose, so let’s study this.’”

The injection technique involves targeting the midline level of the connecting line between left and right medial canthal ligaments with a 90-degree injection angle with bone contact, as well as the medial and inferior margin of eyebrows with a 45-degree injection angle in relation to midline with frontal bone contact. These three points are located inferior to the traditional (on-label) glabellar frown line injections used to treat the frontalis and the brow depressors.

The researchers used the 5-point glabellar line severity scale to evaluate the time of effect onset and the injection-related outcome 120 days after the treatment in 27 men and 78 women. They found that the onset of the neuromodulator effect occurred in an average of 3.5 days, and no adverse events such as eyebrow ptosis, upper eyelid ptosis, medial eyebrow ptosis, and lateral frontalis hyperactivity occurred during the study period.

“If you inject the origin of these muscles, you can get a brow lift with this technique by avoiding frontalis altogether,” Dr. Green said. “The caveat is, it’s so great at lifting the brows that if you treat the forehead, you may create a midline horizontal ‘shelf’ like I’ve never seen before, where the eyebrows elevate into an immobile superior frontalis.”

To avoid this when treating the forehead as well, he’s learned to split the dose of neuromodulator. “If I was injecting 5 units in the procerus before, I’ll do 2.5 units on nasal bone at the insertion of the muscle and then 2.5 units higher up in the traditional midline procerus injection site,” Dr. Green said.

“Same with the corrugators,” he continued. “Then, remember to inject more superficially in the lateral part, the tail of the corrugators, because the tail of the corrugators is inserting into the undersurface of the dermis. That’s why you see that skin puckering in the lateral brows when people frown. You’re pretty safe to chase that laterally if the brow’s already flat as in men, but I caution you [not] to do that in women, because you may flatten the brow.”

Dr. Green said that he is aware of two cases of lid ptosis from the 3-point technique, one of which happened to him.

“When you’re on the bone with your thumb you can feel that liquid traveling along the bone,” he said. “It can travel all the way to the midline pupil where the levator palpebrae superioris muscle is. I now don’t come in contact with bone with my corrugator origin injections, but rather float the needle a couple of millimeters off bone (in muscle) to hopefully prevent that from happening. Alternatively, some people will compress the brow along frontal bone lateral to that corrugator injection site while they’re injecting to prevent backflow of the neuromodulator.”

Dr. Green reported having received research funding and/or consulting fees from many device and pharmaceutical companies.

Among Hispanic/Latinx patients with alopecia areata, the mean age at diagnosis was 33 years, 24% had concomitant atopy, and 18% had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis.

Those are among key findings from a retrospective analysis of Hispanic/Latinx patients at the University of California, Irvine (UCI) by Natasha Mesinkovska, MD, PhD, of UCI’s department of dermatology, and her coauthors. The findings were published online in the Journal of the American Academy of Dermatology.

A recent study examined the epidemiology of alopecia areata (AA) in Black patients, wrote Dr. Mesinkovska and coauthors Celine Phong, a UCI medical student, and Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C. “A similar unmet need exists to describe the characteristics of AA in Hispanic/Latinx (H/L) patients, the prevalent majority in California,” they added.

Drawing from chart reviews, ICD codes, and documented physical exams, they retrospectively identified 197 Hispanic/Latinx patients diagnosed with AA at UCI between 2015 and 2022, including alopecia totalis and alopecia universalis.

Nearly two-thirds of patients with alopecia were female (63%), and their mean age at diagnosis was 33 years. Most patients (79%) presented with patchy pattern AA, 13% had diffuse pattern AA, and only 12% had eyebrow, eyelash, or beard involvement. The most common comorbidity in patients overall was atopy (24%), including allergic rhinitis (12%), asthma (10%), and/or atopic dermatitis (7%).

The authors found that 18% of patients had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis (9%) and thyroid disease (6%). No patients had celiac disease, myasthenia gravis, or inflammatory bowel disease, but 43% had another dermatologic condition.

In other findings, 22% of patients had vitamin D deficiency, 20% had hyperlipidemia, 18% had obesity, 16% had gastroesophageal reflux disease, and 12% had anemia. At the same time, depression, anxiety, or sleep disorders were identified in 14% of patients.

“Interestingly, the most common autoimmune comorbidity in H/L was rheumatoid arthritis, compared to thyroid disease in Black patients and overall AA patients,” the authors wrote. “This finding may be a reflection of a larger trend, as rheumatoid arthritis in the H/L population has been on the rise.”

The authors acknowledged certain limitations of the study including its small sample size and lack of a control group, and reported having no financial disclosures.

Among Hispanic/Latinx patients with alopecia areata, the mean age at diagnosis was 33 years, 24% had concomitant atopy, and 18% had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis.

Those are among key findings from a retrospective analysis of Hispanic/Latinx patients at the University of California, Irvine (UCI) by Natasha Mesinkovska, MD, PhD, of UCI’s department of dermatology, and her coauthors. The findings were published online in the Journal of the American Academy of Dermatology.

A recent study examined the epidemiology of alopecia areata (AA) in Black patients, wrote Dr. Mesinkovska and coauthors Celine Phong, a UCI medical student, and Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C. “A similar unmet need exists to describe the characteristics of AA in Hispanic/Latinx (H/L) patients, the prevalent majority in California,” they added.

Drawing from chart reviews, ICD codes, and documented physical exams, they retrospectively identified 197 Hispanic/Latinx patients diagnosed with AA at UCI between 2015 and 2022, including alopecia totalis and alopecia universalis.

Nearly two-thirds of patients with alopecia were female (63%), and their mean age at diagnosis was 33 years. Most patients (79%) presented with patchy pattern AA, 13% had diffuse pattern AA, and only 12% had eyebrow, eyelash, or beard involvement. The most common comorbidity in patients overall was atopy (24%), including allergic rhinitis (12%), asthma (10%), and/or atopic dermatitis (7%).

The authors found that 18% of patients had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis (9%) and thyroid disease (6%). No patients had celiac disease, myasthenia gravis, or inflammatory bowel disease, but 43% had another dermatologic condition.

In other findings, 22% of patients had vitamin D deficiency, 20% had hyperlipidemia, 18% had obesity, 16% had gastroesophageal reflux disease, and 12% had anemia. At the same time, depression, anxiety, or sleep disorders were identified in 14% of patients.

“Interestingly, the most common autoimmune comorbidity in H/L was rheumatoid arthritis, compared to thyroid disease in Black patients and overall AA patients,” the authors wrote. “This finding may be a reflection of a larger trend, as rheumatoid arthritis in the H/L population has been on the rise.”

The authors acknowledged certain limitations of the study including its small sample size and lack of a control group, and reported having no financial disclosures.

Among Hispanic/Latinx patients with alopecia areata, the mean age at diagnosis was 33 years, 24% had concomitant atopy, and 18% had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis.

Those are among key findings from a retrospective analysis of Hispanic/Latinx patients at the University of California, Irvine (UCI) by Natasha Mesinkovska, MD, PhD, of UCI’s department of dermatology, and her coauthors. The findings were published online in the Journal of the American Academy of Dermatology.

A recent study examined the epidemiology of alopecia areata (AA) in Black patients, wrote Dr. Mesinkovska and coauthors Celine Phong, a UCI medical student, and Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C. “A similar unmet need exists to describe the characteristics of AA in Hispanic/Latinx (H/L) patients, the prevalent majority in California,” they added.

Drawing from chart reviews, ICD codes, and documented physical exams, they retrospectively identified 197 Hispanic/Latinx patients diagnosed with AA at UCI between 2015 and 2022, including alopecia totalis and alopecia universalis.

Nearly two-thirds of patients with alopecia were female (63%), and their mean age at diagnosis was 33 years. Most patients (79%) presented with patchy pattern AA, 13% had diffuse pattern AA, and only 12% had eyebrow, eyelash, or beard involvement. The most common comorbidity in patients overall was atopy (24%), including allergic rhinitis (12%), asthma (10%), and/or atopic dermatitis (7%).

The authors found that 18% of patients had one or more coexisting autoimmune conditions, most commonly rheumatoid arthritis (9%) and thyroid disease (6%). No patients had celiac disease, myasthenia gravis, or inflammatory bowel disease, but 43% had another dermatologic condition.

In other findings, 22% of patients had vitamin D deficiency, 20% had hyperlipidemia, 18% had obesity, 16% had gastroesophageal reflux disease, and 12% had anemia. At the same time, depression, anxiety, or sleep disorders were identified in 14% of patients.

“Interestingly, the most common autoimmune comorbidity in H/L was rheumatoid arthritis, compared to thyroid disease in Black patients and overall AA patients,” the authors wrote. “This finding may be a reflection of a larger trend, as rheumatoid arthritis in the H/L population has been on the rise.”

The authors acknowledged certain limitations of the study including its small sample size and lack of a control group, and reported having no financial disclosures.