Dermatology

THE COMPARISON

A A 27-year-old Hispanic woman with comedonal and inflammatory acne. Erythema is prominent around the inflammatory lesions. Note the pustule on the cheek surrounded by pink color.

B A teenaged Black boy with acne papules and pustules on the face. There are comedones, hyperpigmented macules, and pustules on the cheek.

C A teenaged Black girl with pomade acne. The patient used various hair care products, which obstructed the pilosebaceous units on the forehead.

Epidemiology

Acne is a leading dermatologic condition in individuals with skin of color in the United States.¹

Key clinical features in people with darker skin tones include:

• erythematous or hyperpigmented papules or comedones
• hyperpigmented macules and postinflammatory hyperpigmentation (PIH)
• increased risk for keloidal scars.²

Worth noting

• Patients with darker skin tones may be more concerned with the dark marks (also referred to as scars or manchas in Spanish) than the acne itself. This PIH may be viewed by patients as the major problem.
• Acne medications such as azelaic acid and some retinoids (when applied appropriately) can treat both acne and PIH.³
• Irritation from topical acne medications, including retinoid dermatitis, may lead to more PIH. Using noncomedogenic moisturizers and applying medication appropriately (ie, a pea-sized amount of topical retinoid per application) may help limit irritation.^4,5
• One type of acne seen more commonly, although not exclusively, in Black patients is pomade acne, which principally appears on the forehead and is associated with use of hair care and styling products (FIGURE C).

Health disparity highlight

Disparities in access to health care exist for those with dermatologic concerns. According to one study, African American (28.5%) and Hispanic patients (23.9%) were less likely to be seen by a dermatologist solely for the diagnosis of a dermatologic condition compared to Asian and Pacific Islander patients (36.7%) or White patients (43.2%).¹ Noting that isotretinoin is the most potent systemic therapy for severe cystic acne vulgaris, Bell et al⁶ reported that Black patients had lower odds of receiving isotretinoin compared to White patients. Hispanic patients had lower odds of receiving a topical retinoid, tretinoin, than non-Hispanic patients.⁶

THE COMPARISON

A A 27-year-old Hispanic woman with comedonal and inflammatory acne. Erythema is prominent around the inflammatory lesions. Note the pustule on the cheek surrounded by pink color.

B A teenaged Black boy with acne papules and pustules on the face. There are comedones, hyperpigmented macules, and pustules on the cheek.

C A teenaged Black girl with pomade acne. The patient used various hair care products, which obstructed the pilosebaceous units on the forehead.

Epidemiology

Acne is a leading dermatologic condition in individuals with skin of color in the United States.¹

Key clinical features in people with darker skin tones include:

• erythematous or hyperpigmented papules or comedones
• hyperpigmented macules and postinflammatory hyperpigmentation (PIH)
• increased risk for keloidal scars.²

Worth noting

• Patients with darker skin tones may be more concerned with the dark marks (also referred to as scars or manchas in Spanish) than the acne itself. This PIH may be viewed by patients as the major problem.
• Acne medications such as azelaic acid and some retinoids (when applied appropriately) can treat both acne and PIH.³
• Irritation from topical acne medications, including retinoid dermatitis, may lead to more PIH. Using noncomedogenic moisturizers and applying medication appropriately (ie, a pea-sized amount of topical retinoid per application) may help limit irritation.^4,5
• One type of acne seen more commonly, although not exclusively, in Black patients is pomade acne, which principally appears on the forehead and is associated with use of hair care and styling products (FIGURE C).

Health disparity highlight

Disparities in access to health care exist for those with dermatologic concerns. According to one study, African American (28.5%) and Hispanic patients (23.9%) were less likely to be seen by a dermatologist solely for the diagnosis of a dermatologic condition compared to Asian and Pacific Islander patients (36.7%) or White patients (43.2%).¹ Noting that isotretinoin is the most potent systemic therapy for severe cystic acne vulgaris, Bell et al⁶ reported that Black patients had lower odds of receiving isotretinoin compared to White patients. Hispanic patients had lower odds of receiving a topical retinoid, tretinoin, than non-Hispanic patients.⁶

THE COMPARISON

A A 27-year-old Hispanic woman with comedonal and inflammatory acne. Erythema is prominent around the inflammatory lesions. Note the pustule on the cheek surrounded by pink color.

B A teenaged Black boy with acne papules and pustules on the face. There are comedones, hyperpigmented macules, and pustules on the cheek.

C A teenaged Black girl with pomade acne. The patient used various hair care products, which obstructed the pilosebaceous units on the forehead.

Epidemiology

Acne is a leading dermatologic condition in individuals with skin of color in the United States.¹

Key clinical features in people with darker skin tones include:

• erythematous or hyperpigmented papules or comedones
• hyperpigmented macules and postinflammatory hyperpigmentation (PIH)
• increased risk for keloidal scars.²

Worth noting

• Patients with darker skin tones may be more concerned with the dark marks (also referred to as scars or manchas in Spanish) than the acne itself. This PIH may be viewed by patients as the major problem.
• Acne medications such as azelaic acid and some retinoids (when applied appropriately) can treat both acne and PIH.³
• Irritation from topical acne medications, including retinoid dermatitis, may lead to more PIH. Using noncomedogenic moisturizers and applying medication appropriately (ie, a pea-sized amount of topical retinoid per application) may help limit irritation.^4,5
• One type of acne seen more commonly, although not exclusively, in Black patients is pomade acne, which principally appears on the forehead and is associated with use of hair care and styling products (FIGURE C).

Health disparity highlight

Disparities in access to health care exist for those with dermatologic concerns. According to one study, African American (28.5%) and Hispanic patients (23.9%) were less likely to be seen by a dermatologist solely for the diagnosis of a dermatologic condition compared to Asian and Pacific Islander patients (36.7%) or White patients (43.2%).¹ Noting that isotretinoin is the most potent systemic therapy for severe cystic acne vulgaris, Bell et al⁶ reported that Black patients had lower odds of receiving isotretinoin compared to White patients. Hispanic patients had lower odds of receiving a topical retinoid, tretinoin, than non-Hispanic patients.⁶

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

In the clinical opinion of Alex G. Ortega-Loayza, MD, MCR, few absolutes drive the initial assessment of patients who present with skin ulcers.

While lower-extremity ulcers stem from vascular, neuropathic, or pressure-related causes in about 70% of cases, an estimated 20% of cases are atypical, and another 10% are inconclusive. The causes can be neoplastic, infectious, inflammatory, vasculopathic, external, and genetic. “Sometimes they can be of mixed etiology, which make them even more complicated to heal,” Dr. Ortega-Loayza, of the department of dermatology at Oregon Health & Science University, Portland, said during the annual meeting of the Pacific Dermatologic Association.

In a study published in 2019, he and his colleagues at four academic hospitals evaluated characteristics and diagnoses of ulcers in 274 patients with skin ulcers in inpatient dermatology consultation services between July 2015 and July 2018. Most primary teams requesting the consultation (93%) were from nonsurgical specialties. The median age of these patients was 54 years, 45% were male, and 50% had lower-extremity ulcers. Nearly two-thirds of the ulcers (62%) were chronic in nature, while the remaining 38% were acute. The skin ulcer was the chief reason for admission in 49% of cases and 66% were admitted through the ED. In addition, 11% had a superinfected skin ulcer.

The top three etiologies rendered by dermatologists after assessing these patients were pyoderma gangrenosum (17%), infection (13%), and exogenous causes (12%); another 12% remained diagnostically inconclusive after consultation. Diagnostic agreements between the primary team requesting the consultation and the dermatologist were poor to modest.

These data highlights the role of the dermatologists in the workup of skin ulcers of unknown etiology.

“The diagnosis of skin ulcers can be challenging,” Dr. Ortega-Loayza said. “Subjective factors playing a role in the diagnosis of skin ulcers include the type of level of training/experience you’ve had and general awareness and education about skin ulcers.” In addition, there is also a lack of gold-standard diagnostic criteria for atypical/inflammatory ulcers and a lack of specificity of ancillary testing, such as for pyoderma gangrenosum.

Dr. Ortega-Loayza’s basic workup is based on the review of systems and the patient’s comorbidities. Blood work may include CBC, comprehensive metabolic panel, erythrocyte sedimentation rate/C-reactive protein, glucose-6-phosphate dehydrogenase, albumin/prealbumin, autoimmune panels, and hypercoagulable panels. He may order a skin biopsy with H&E staining and microbiological studies, superficial bacterial wound cultures, and vascular studies, such as ankle brachial index (ABI) and chronic venous reflux tests, and Doppler ultrasound, and he might consider an angiogram for certain type of ulcers. Additional imaging studies may include x-ray, CT scan, and/or MRI.

The four key factors to control in patients with skin ulcers, he continued, include effective management of edema (such as compression garments depending on the results of the vascular studies); infection (with topical/oral antibiotics and debridement); the wound microenvironment (with wound dressings), and pain (mainly with nonopioids). “In my practice, we tend to do multilayered compression,” he said. “This can be two- or four-layer. I do light compression if the patient has peripheral arterial disease. I always bring in the patient 2 days later to check on them, or do a telehealth visit, to make sure they are not developing any worsening of the ulcers.”

Infections can be managed with topical antimicrobials such as metronidazole 1% gel and cadexomer iodine. “Iodine can also help dry the wound when you need to do so,” said Dr. Ortega-Loayza, who directs a pyoderma gangrenosum clinic at OHSU. “Debridement can be done with a curette or with commercially available enzymatic products such as Collagenase, PluroGel, and MediHoney.”

When the ulcer is in an active phase (characterized by significant amount of drainage and erythema), he uses one or more of the following products to control the wound microenvironment: zinc oxide, an antimicrobial dressing, a hyperabsorbent dressing, an abdominal pad, and compression.

During the healing phase, with evidence of re-epithelization, he tends to use more foam dressings and continues with compression. His preferred options for managing pain associated with ulcers are medications to control neuropathic pain including initially gabapentin (100 mg-300 mg at bedtime), pregabalin (75 mg twice a day), or duloxetine (extended release, 30 mg once a day). All of these medications can be titrated up based on patients’ needs. Foam dressings with ibuprofen can also provide comfort, he said.

Dr. Ortega-Loayza also provided a few clinical pearls highlighting the role and utility of interleukin-23 inhibitors in the management of patients with pyoderma gangrenosum, oral vitamin K in patients with calciphylaxis, and stanozolol for lipodermatosclerosis. He is also leading the first open-label trial testing a Janus kinase inhibitor – baricitinib – as a treatment for patients with pyoderma gangrenosum.

Dr. Ortega-Loayza disclosed that he is a consultant to Genentech and Guidepoint and is a member of the advisory board for Bristol-Myers Squibb, Boehringer Ingelheim, and Janssen. He also has received research support from Lilly.

dbrunk@mdedge.com

In the clinical opinion of Alex G. Ortega-Loayza, MD, MCR, few absolutes drive the initial assessment of patients who present with skin ulcers.

While lower-extremity ulcers stem from vascular, neuropathic, or pressure-related causes in about 70% of cases, an estimated 20% of cases are atypical, and another 10% are inconclusive. The causes can be neoplastic, infectious, inflammatory, vasculopathic, external, and genetic. “Sometimes they can be of mixed etiology, which make them even more complicated to heal,” Dr. Ortega-Loayza, of the department of dermatology at Oregon Health & Science University, Portland, said during the annual meeting of the Pacific Dermatologic Association.

In a study published in 2019, he and his colleagues at four academic hospitals evaluated characteristics and diagnoses of ulcers in 274 patients with skin ulcers in inpatient dermatology consultation services between July 2015 and July 2018. Most primary teams requesting the consultation (93%) were from nonsurgical specialties. The median age of these patients was 54 years, 45% were male, and 50% had lower-extremity ulcers. Nearly two-thirds of the ulcers (62%) were chronic in nature, while the remaining 38% were acute. The skin ulcer was the chief reason for admission in 49% of cases and 66% were admitted through the ED. In addition, 11% had a superinfected skin ulcer.

The top three etiologies rendered by dermatologists after assessing these patients were pyoderma gangrenosum (17%), infection (13%), and exogenous causes (12%); another 12% remained diagnostically inconclusive after consultation. Diagnostic agreements between the primary team requesting the consultation and the dermatologist were poor to modest.

These data highlights the role of the dermatologists in the workup of skin ulcers of unknown etiology.

“The diagnosis of skin ulcers can be challenging,” Dr. Ortega-Loayza said. “Subjective factors playing a role in the diagnosis of skin ulcers include the type of level of training/experience you’ve had and general awareness and education about skin ulcers.” In addition, there is also a lack of gold-standard diagnostic criteria for atypical/inflammatory ulcers and a lack of specificity of ancillary testing, such as for pyoderma gangrenosum.

Dr. Ortega-Loayza’s basic workup is based on the review of systems and the patient’s comorbidities. Blood work may include CBC, comprehensive metabolic panel, erythrocyte sedimentation rate/C-reactive protein, glucose-6-phosphate dehydrogenase, albumin/prealbumin, autoimmune panels, and hypercoagulable panels. He may order a skin biopsy with H&E staining and microbiological studies, superficial bacterial wound cultures, and vascular studies, such as ankle brachial index (ABI) and chronic venous reflux tests, and Doppler ultrasound, and he might consider an angiogram for certain type of ulcers. Additional imaging studies may include x-ray, CT scan, and/or MRI.

The four key factors to control in patients with skin ulcers, he continued, include effective management of edema (such as compression garments depending on the results of the vascular studies); infection (with topical/oral antibiotics and debridement); the wound microenvironment (with wound dressings), and pain (mainly with nonopioids). “In my practice, we tend to do multilayered compression,” he said. “This can be two- or four-layer. I do light compression if the patient has peripheral arterial disease. I always bring in the patient 2 days later to check on them, or do a telehealth visit, to make sure they are not developing any worsening of the ulcers.”

Infections can be managed with topical antimicrobials such as metronidazole 1% gel and cadexomer iodine. “Iodine can also help dry the wound when you need to do so,” said Dr. Ortega-Loayza, who directs a pyoderma gangrenosum clinic at OHSU. “Debridement can be done with a curette or with commercially available enzymatic products such as Collagenase, PluroGel, and MediHoney.”

When the ulcer is in an active phase (characterized by significant amount of drainage and erythema), he uses one or more of the following products to control the wound microenvironment: zinc oxide, an antimicrobial dressing, a hyperabsorbent dressing, an abdominal pad, and compression.

During the healing phase, with evidence of re-epithelization, he tends to use more foam dressings and continues with compression. His preferred options for managing pain associated with ulcers are medications to control neuropathic pain including initially gabapentin (100 mg-300 mg at bedtime), pregabalin (75 mg twice a day), or duloxetine (extended release, 30 mg once a day). All of these medications can be titrated up based on patients’ needs. Foam dressings with ibuprofen can also provide comfort, he said.

Dr. Ortega-Loayza also provided a few clinical pearls highlighting the role and utility of interleukin-23 inhibitors in the management of patients with pyoderma gangrenosum, oral vitamin K in patients with calciphylaxis, and stanozolol for lipodermatosclerosis. He is also leading the first open-label trial testing a Janus kinase inhibitor – baricitinib – as a treatment for patients with pyoderma gangrenosum.

Dr. Ortega-Loayza disclosed that he is a consultant to Genentech and Guidepoint and is a member of the advisory board for Bristol-Myers Squibb, Boehringer Ingelheim, and Janssen. He also has received research support from Lilly.

dbrunk@mdedge.com

In the clinical opinion of Alex G. Ortega-Loayza, MD, MCR, few absolutes drive the initial assessment of patients who present with skin ulcers.

While lower-extremity ulcers stem from vascular, neuropathic, or pressure-related causes in about 70% of cases, an estimated 20% of cases are atypical, and another 10% are inconclusive. The causes can be neoplastic, infectious, inflammatory, vasculopathic, external, and genetic. “Sometimes they can be of mixed etiology, which make them even more complicated to heal,” Dr. Ortega-Loayza, of the department of dermatology at Oregon Health & Science University, Portland, said during the annual meeting of the Pacific Dermatologic Association.

In a study published in 2019, he and his colleagues at four academic hospitals evaluated characteristics and diagnoses of ulcers in 274 patients with skin ulcers in inpatient dermatology consultation services between July 2015 and July 2018. Most primary teams requesting the consultation (93%) were from nonsurgical specialties. The median age of these patients was 54 years, 45% were male, and 50% had lower-extremity ulcers. Nearly two-thirds of the ulcers (62%) were chronic in nature, while the remaining 38% were acute. The skin ulcer was the chief reason for admission in 49% of cases and 66% were admitted through the ED. In addition, 11% had a superinfected skin ulcer.

The top three etiologies rendered by dermatologists after assessing these patients were pyoderma gangrenosum (17%), infection (13%), and exogenous causes (12%); another 12% remained diagnostically inconclusive after consultation. Diagnostic agreements between the primary team requesting the consultation and the dermatologist were poor to modest.

These data highlights the role of the dermatologists in the workup of skin ulcers of unknown etiology.

“The diagnosis of skin ulcers can be challenging,” Dr. Ortega-Loayza said. “Subjective factors playing a role in the diagnosis of skin ulcers include the type of level of training/experience you’ve had and general awareness and education about skin ulcers.” In addition, there is also a lack of gold-standard diagnostic criteria for atypical/inflammatory ulcers and a lack of specificity of ancillary testing, such as for pyoderma gangrenosum.

Dr. Ortega-Loayza’s basic workup is based on the review of systems and the patient’s comorbidities. Blood work may include CBC, comprehensive metabolic panel, erythrocyte sedimentation rate/C-reactive protein, glucose-6-phosphate dehydrogenase, albumin/prealbumin, autoimmune panels, and hypercoagulable panels. He may order a skin biopsy with H&E staining and microbiological studies, superficial bacterial wound cultures, and vascular studies, such as ankle brachial index (ABI) and chronic venous reflux tests, and Doppler ultrasound, and he might consider an angiogram for certain type of ulcers. Additional imaging studies may include x-ray, CT scan, and/or MRI.

The four key factors to control in patients with skin ulcers, he continued, include effective management of edema (such as compression garments depending on the results of the vascular studies); infection (with topical/oral antibiotics and debridement); the wound microenvironment (with wound dressings), and pain (mainly with nonopioids). “In my practice, we tend to do multilayered compression,” he said. “This can be two- or four-layer. I do light compression if the patient has peripheral arterial disease. I always bring in the patient 2 days later to check on them, or do a telehealth visit, to make sure they are not developing any worsening of the ulcers.”

Infections can be managed with topical antimicrobials such as metronidazole 1% gel and cadexomer iodine. “Iodine can also help dry the wound when you need to do so,” said Dr. Ortega-Loayza, who directs a pyoderma gangrenosum clinic at OHSU. “Debridement can be done with a curette or with commercially available enzymatic products such as Collagenase, PluroGel, and MediHoney.”

When the ulcer is in an active phase (characterized by significant amount of drainage and erythema), he uses one or more of the following products to control the wound microenvironment: zinc oxide, an antimicrobial dressing, a hyperabsorbent dressing, an abdominal pad, and compression.

During the healing phase, with evidence of re-epithelization, he tends to use more foam dressings and continues with compression. His preferred options for managing pain associated with ulcers are medications to control neuropathic pain including initially gabapentin (100 mg-300 mg at bedtime), pregabalin (75 mg twice a day), or duloxetine (extended release, 30 mg once a day). All of these medications can be titrated up based on patients’ needs. Foam dressings with ibuprofen can also provide comfort, he said.

Dr. Ortega-Loayza also provided a few clinical pearls highlighting the role and utility of interleukin-23 inhibitors in the management of patients with pyoderma gangrenosum, oral vitamin K in patients with calciphylaxis, and stanozolol for lipodermatosclerosis. He is also leading the first open-label trial testing a Janus kinase inhibitor – baricitinib – as a treatment for patients with pyoderma gangrenosum.

Dr. Ortega-Loayza disclosed that he is a consultant to Genentech and Guidepoint and is a member of the advisory board for Bristol-Myers Squibb, Boehringer Ingelheim, and Janssen. He also has received research support from Lilly.

dbrunk@mdedge.com

A solitary dark lesion on the back of an adult is worrisome for melanoma. A scoop-shave biopsy was ordered with the aim of achieving a 1- to 3-mm margin. The biopsy identified the lesion as a benign pigmented seborrheic keratosis (SK).

SKs are a group of common, keratinocyte neoplasms that can occur in large numbers on a patient. They may meet many of the ABCDE criteria (Asymmetry, Border irregularity, Color [varying shades or deep black color], Diameter > 6 mm, or Evolving/changing) used to grossly identify potential melanomas. It is worth noting that not all dark-pigmented lesions arise from melanocytes. In this instance, the dark SK is made of keratinocytes that had accumulated melanin.

Dermoscopy usually helps distinguish SKs from melanocytic neoplasm, which would include nevi and melanoma. Melanocytic lesions (whether benign nevi or malignant melanoma) will display a pigment network, globules, streaks, homogeneous blue or tan color, or characteristic vascular findings. SKs, on the other hand, often demonstrate sharply demarcated borders, milia-like cysts or comedo-like openings, and hairpin vessels.

Both the clinical and dermoscopic photos in this case showed a sharply demarcated border, lack of network, and an absence of any vascular markings. The central scale crust did not exclude a melanocytic lesion and there were peripheral small black dots that could have been asymmetrical globules; however, the biopsy negated those clinical concerns.

Dermoscopy improves diagnostic specificity, but not perfectly. The number of benign lesions biopsied for every malignant lesion confirmed decreases from about 18 without dermoscopy to 8 or fewer for the most experienced dermoscopy practitioners.¹ This case highlights one of many instances of a clinically and dermoscopically suspicious lesion that ultimately was benign.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

A solitary dark lesion on the back of an adult is worrisome for melanoma. A scoop-shave biopsy was ordered with the aim of achieving a 1- to 3-mm margin. The biopsy identified the lesion as a benign pigmented seborrheic keratosis (SK).

SKs are a group of common, keratinocyte neoplasms that can occur in large numbers on a patient. They may meet many of the ABCDE criteria (Asymmetry, Border irregularity, Color [varying shades or deep black color], Diameter > 6 mm, or Evolving/changing) used to grossly identify potential melanomas. It is worth noting that not all dark-pigmented lesions arise from melanocytes. In this instance, the dark SK is made of keratinocytes that had accumulated melanin.

Dermoscopy usually helps distinguish SKs from melanocytic neoplasm, which would include nevi and melanoma. Melanocytic lesions (whether benign nevi or malignant melanoma) will display a pigment network, globules, streaks, homogeneous blue or tan color, or characteristic vascular findings. SKs, on the other hand, often demonstrate sharply demarcated borders, milia-like cysts or comedo-like openings, and hairpin vessels.

Both the clinical and dermoscopic photos in this case showed a sharply demarcated border, lack of network, and an absence of any vascular markings. The central scale crust did not exclude a melanocytic lesion and there were peripheral small black dots that could have been asymmetrical globules; however, the biopsy negated those clinical concerns.

Dermoscopy improves diagnostic specificity, but not perfectly. The number of benign lesions biopsied for every malignant lesion confirmed decreases from about 18 without dermoscopy to 8 or fewer for the most experienced dermoscopy practitioners.¹ This case highlights one of many instances of a clinically and dermoscopically suspicious lesion that ultimately was benign.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

A solitary dark lesion on the back of an adult is worrisome for melanoma. A scoop-shave biopsy was ordered with the aim of achieving a 1- to 3-mm margin. The biopsy identified the lesion as a benign pigmented seborrheic keratosis (SK).

SKs are a group of common, keratinocyte neoplasms that can occur in large numbers on a patient. They may meet many of the ABCDE criteria (Asymmetry, Border irregularity, Color [varying shades or deep black color], Diameter > 6 mm, or Evolving/changing) used to grossly identify potential melanomas. It is worth noting that not all dark-pigmented lesions arise from melanocytes. In this instance, the dark SK is made of keratinocytes that had accumulated melanin.

Dermoscopy usually helps distinguish SKs from melanocytic neoplasm, which would include nevi and melanoma. Melanocytic lesions (whether benign nevi or malignant melanoma) will display a pigment network, globules, streaks, homogeneous blue or tan color, or characteristic vascular findings. SKs, on the other hand, often demonstrate sharply demarcated borders, milia-like cysts or comedo-like openings, and hairpin vessels.

Both the clinical and dermoscopic photos in this case showed a sharply demarcated border, lack of network, and an absence of any vascular markings. The central scale crust did not exclude a melanocytic lesion and there were peripheral small black dots that could have been asymmetrical globules; however, the biopsy negated those clinical concerns.

Dermoscopy improves diagnostic specificity, but not perfectly. The number of benign lesions biopsied for every malignant lesion confirmed decreases from about 18 without dermoscopy to 8 or fewer for the most experienced dermoscopy practitioners.¹ This case highlights one of many instances of a clinically and dermoscopically suspicious lesion that ultimately was benign.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

A 2-YEAR-OLD BOY presented to the emergency room with a 1-day history of a diffuse, mildly pruritic rash and swelling of his knees, ankles, and feet following treatment of acute otitis media with amoxicillin for the previous 8 days. He was mildly febrile and consolable, but he was refusing to walk. His medical history was unremarkable.

Physical examination revealed erythematous annular wheals on his chest, face, back, and extremities. Lymphadenopathy and mucous membrane involvement were not present. A complete blood count (CBC) with differential, inflammatory marker tests, and a comprehensive metabolic panel were ordered. Given the joint swelling and rash, the patient was admitted for observation.

During his second day in the hospital, his skin lesions enlarged and several formed dusky blue centers (FIGURE 1A). He also developed swelling of his hands (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Urticaria multiforme

The patient’s lab work came back within normal range, except for an elevated white blood cell count (19,700/mm³; reference range, 4500-13,500/mm³). His mild systemic symptoms, skin lesions without blistering or necrosis, acral edema, and the absence of lymphadenopathy pointed to a diagnosis of urticaria multiforme.

Children with urticaria multiforme may have significant edema of the feet and may find walking difficult; this should not be confused with arthritis or arthralgias.

Urticaria multiforme, also called acute annular urticaria or acute urticarial hypersensitivity syndrome, is a histamine-mediated hypersensitivity reaction characterized by transient annular, polycyclic, urticarial lesions with central ecchymosis. The incidence and prevalence are not known. Urticaria multiforme is considered common, but it is frequently misdiagnosed.¹ It typically manifests in children ages 4 months to 4 years and begins with small erythematous macules, papules, and plaques that progress to large blanchable wheals with dusky blue centers.^1-3 Lesions are usually located on the face, trunk, and extremities and are often pruritic (60%-94%).^1-3 Individual lesions last less than 24 hours, but new ones may appear. The rash generally lasts 2 to 12 days.^1,3

Patients often report a preceding viral illness, otitis media, recent use of antibiotics, or recent immunizations. Dermatographism due to mast cell–mediated cutaneous hypersensitivity at sites of minor skin trauma is common (44%).¹ Patients often have associated facial or acral edema (72%).¹ Children with significant edema of the feet may find walking difficult, which should not be confused with arthritis or arthralgias. Generally, patients are nontoxic in appearance, and systemic symptoms are limited to a low-grade fever.^1-3

The diagnosis is made clinically and should not require a skin biopsy or extensive laboratory testing.When performed, laboratory studies, including CBC, erythrocyte sedimentation rate, C-reactive protein, and urinalysis are routinely normal.

Erythema multiforme and urticarial vasculitis are part of the differential

The differential diagnosis in this case includes erythema multiforme, Henoch-Schönlein purpura, serum sickness-like reaction, and urticarial vasculitis (TABLE^1,2,4).

Continue to: Erythema multiforme

Erythema multiforme is a common misdiagnosis in patients with urticaria multiforme.^1,2 The erythema multiforme rash has a “target” lesion with outer erythema and central ecchymosis, which may develop blisters or necrosis. Lesions are fixed and last 2 to 3 weeks. Unlike urticaria multiforme, patients with erythema multiforme commonly have mucous membrane erosions and occasionally ulcerations. Facial and acral edema is rare. Treatment is largely symptomatic and can include glucocorticoids. Antiviral medications may be used to treat recurrences.^1,2

Henoch-Schönlein purpura is an immunoglobulin A–mediated vasculitis that affects the skin, gastrointestinal tract, and joints.^4,5 Patients often present with arthralgias, gastrointestinal symptoms such as abdominal pain and bleeding, and a nonpruritic, erythematous rash that progresses to palpable purpura in dependent areas of the body. Treatment is generally symptomatic, but steroids may be used in severe cases.^4,5

Serum sickness-like reaction can manifest with angioedema and a similar urticarial rash (with central clearing) that lasts 1 to 6 weeks.^1,2,6,7 However, patients tend to have a high-grade fever, arthralgias, myalgias, and lymphadenopathy while dermatographism is absent. Treatment includes discontinuing the offending agent and the use of H1 and H2 antihistamines and steroids, in severe cases.

Urticarial vasculitis manifests as plaques or wheals lasting 1 to 7 days that may cause burning and pain but not pruritis.^2,5 Purpura or hypopigmentation may develop as the hives resolve. Angioedema and arthralgias are common, but dermatographism is not present. Triggers include infections, autoimmune disease, malignancy, and the use of certain medications. H1 and H2 blockers and nonsteroidal anti-inflammatory agents are first-line therapy.²

Step 1: Discontinue offending agents; Step 2: Recommend antihistamines

Treatment consists of discontinuing any offending agent (if suspected) and using systemic H1 or H2 antihistamines for symptom relief. Systemic steroids should only be given in refractory cases.

Continue to: Our patient's amoxicillin

Our patient’s amoxicillin was discontinued, and he was started on a 14-day course of cetirizine 5 mg bid and hydroxyzine 10 mg at bedtime. He was also started on triamcinolone 0.1% cream to be applied twice daily for 1 week. During his 3-day hospital stay, his fever resolved and his rash and edema improved.

During an outpatient follow-up visit with a pediatric dermatologist 2 weeks after discharge, the patient’s rash was still present and dermatographism was noted. In light of this, his parents were instructed to continue giving the cetirizine and hydroxyzine once daily for an additional 2 weeks and to return as needed.

A 2-YEAR-OLD BOY presented to the emergency room with a 1-day history of a diffuse, mildly pruritic rash and swelling of his knees, ankles, and feet following treatment of acute otitis media with amoxicillin for the previous 8 days. He was mildly febrile and consolable, but he was refusing to walk. His medical history was unremarkable.

Physical examination revealed erythematous annular wheals on his chest, face, back, and extremities. Lymphadenopathy and mucous membrane involvement were not present. A complete blood count (CBC) with differential, inflammatory marker tests, and a comprehensive metabolic panel were ordered. Given the joint swelling and rash, the patient was admitted for observation.

During his second day in the hospital, his skin lesions enlarged and several formed dusky blue centers (FIGURE 1A). He also developed swelling of his hands (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Urticaria multiforme

The patient’s lab work came back within normal range, except for an elevated white blood cell count (19,700/mm³; reference range, 4500-13,500/mm³). His mild systemic symptoms, skin lesions without blistering or necrosis, acral edema, and the absence of lymphadenopathy pointed to a diagnosis of urticaria multiforme.

Children with urticaria multiforme may have significant edema of the feet and may find walking difficult; this should not be confused with arthritis or arthralgias.

Urticaria multiforme, also called acute annular urticaria or acute urticarial hypersensitivity syndrome, is a histamine-mediated hypersensitivity reaction characterized by transient annular, polycyclic, urticarial lesions with central ecchymosis. The incidence and prevalence are not known. Urticaria multiforme is considered common, but it is frequently misdiagnosed.¹ It typically manifests in children ages 4 months to 4 years and begins with small erythematous macules, papules, and plaques that progress to large blanchable wheals with dusky blue centers.^1-3 Lesions are usually located on the face, trunk, and extremities and are often pruritic (60%-94%).^1-3 Individual lesions last less than 24 hours, but new ones may appear. The rash generally lasts 2 to 12 days.^1,3

Patients often report a preceding viral illness, otitis media, recent use of antibiotics, or recent immunizations. Dermatographism due to mast cell–mediated cutaneous hypersensitivity at sites of minor skin trauma is common (44%).¹ Patients often have associated facial or acral edema (72%).¹ Children with significant edema of the feet may find walking difficult, which should not be confused with arthritis or arthralgias. Generally, patients are nontoxic in appearance, and systemic symptoms are limited to a low-grade fever.^1-3

The diagnosis is made clinically and should not require a skin biopsy or extensive laboratory testing.When performed, laboratory studies, including CBC, erythrocyte sedimentation rate, C-reactive protein, and urinalysis are routinely normal.

Erythema multiforme and urticarial vasculitis are part of the differential

The differential diagnosis in this case includes erythema multiforme, Henoch-Schönlein purpura, serum sickness-like reaction, and urticarial vasculitis (TABLE^1,2,4).

Continue to: Erythema multiforme

Erythema multiforme is a common misdiagnosis in patients with urticaria multiforme.^1,2 The erythema multiforme rash has a “target” lesion with outer erythema and central ecchymosis, which may develop blisters or necrosis. Lesions are fixed and last 2 to 3 weeks. Unlike urticaria multiforme, patients with erythema multiforme commonly have mucous membrane erosions and occasionally ulcerations. Facial and acral edema is rare. Treatment is largely symptomatic and can include glucocorticoids. Antiviral medications may be used to treat recurrences.^1,2

Henoch-Schönlein purpura is an immunoglobulin A–mediated vasculitis that affects the skin, gastrointestinal tract, and joints.^4,5 Patients often present with arthralgias, gastrointestinal symptoms such as abdominal pain and bleeding, and a nonpruritic, erythematous rash that progresses to palpable purpura in dependent areas of the body. Treatment is generally symptomatic, but steroids may be used in severe cases.^4,5

Serum sickness-like reaction can manifest with angioedema and a similar urticarial rash (with central clearing) that lasts 1 to 6 weeks.^1,2,6,7 However, patients tend to have a high-grade fever, arthralgias, myalgias, and lymphadenopathy while dermatographism is absent. Treatment includes discontinuing the offending agent and the use of H1 and H2 antihistamines and steroids, in severe cases.

Urticarial vasculitis manifests as plaques or wheals lasting 1 to 7 days that may cause burning and pain but not pruritis.^2,5 Purpura or hypopigmentation may develop as the hives resolve. Angioedema and arthralgias are common, but dermatographism is not present. Triggers include infections, autoimmune disease, malignancy, and the use of certain medications. H1 and H2 blockers and nonsteroidal anti-inflammatory agents are first-line therapy.²

Step 1: Discontinue offending agents; Step 2: Recommend antihistamines

Treatment consists of discontinuing any offending agent (if suspected) and using systemic H1 or H2 antihistamines for symptom relief. Systemic steroids should only be given in refractory cases.

Continue to: Our patient's amoxicillin

Our patient’s amoxicillin was discontinued, and he was started on a 14-day course of cetirizine 5 mg bid and hydroxyzine 10 mg at bedtime. He was also started on triamcinolone 0.1% cream to be applied twice daily for 1 week. During his 3-day hospital stay, his fever resolved and his rash and edema improved.

During an outpatient follow-up visit with a pediatric dermatologist 2 weeks after discharge, the patient’s rash was still present and dermatographism was noted. In light of this, his parents were instructed to continue giving the cetirizine and hydroxyzine once daily for an additional 2 weeks and to return as needed.

A 2-YEAR-OLD BOY presented to the emergency room with a 1-day history of a diffuse, mildly pruritic rash and swelling of his knees, ankles, and feet following treatment of acute otitis media with amoxicillin for the previous 8 days. He was mildly febrile and consolable, but he was refusing to walk. His medical history was unremarkable.

Physical examination revealed erythematous annular wheals on his chest, face, back, and extremities. Lymphadenopathy and mucous membrane involvement were not present. A complete blood count (CBC) with differential, inflammatory marker tests, and a comprehensive metabolic panel were ordered. Given the joint swelling and rash, the patient was admitted for observation.

During his second day in the hospital, his skin lesions enlarged and several formed dusky blue centers (FIGURE 1A). He also developed swelling of his hands (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Urticaria multiforme

The patient’s lab work came back within normal range, except for an elevated white blood cell count (19,700/mm³; reference range, 4500-13,500/mm³). His mild systemic symptoms, skin lesions without blistering or necrosis, acral edema, and the absence of lymphadenopathy pointed to a diagnosis of urticaria multiforme.

Children with urticaria multiforme may have significant edema of the feet and may find walking difficult; this should not be confused with arthritis or arthralgias.

Urticaria multiforme, also called acute annular urticaria or acute urticarial hypersensitivity syndrome, is a histamine-mediated hypersensitivity reaction characterized by transient annular, polycyclic, urticarial lesions with central ecchymosis. The incidence and prevalence are not known. Urticaria multiforme is considered common, but it is frequently misdiagnosed.¹ It typically manifests in children ages 4 months to 4 years and begins with small erythematous macules, papules, and plaques that progress to large blanchable wheals with dusky blue centers.^1-3 Lesions are usually located on the face, trunk, and extremities and are often pruritic (60%-94%).^1-3 Individual lesions last less than 24 hours, but new ones may appear. The rash generally lasts 2 to 12 days.^1,3

Patients often report a preceding viral illness, otitis media, recent use of antibiotics, or recent immunizations. Dermatographism due to mast cell–mediated cutaneous hypersensitivity at sites of minor skin trauma is common (44%).¹ Patients often have associated facial or acral edema (72%).¹ Children with significant edema of the feet may find walking difficult, which should not be confused with arthritis or arthralgias. Generally, patients are nontoxic in appearance, and systemic symptoms are limited to a low-grade fever.^1-3

The diagnosis is made clinically and should not require a skin biopsy or extensive laboratory testing.When performed, laboratory studies, including CBC, erythrocyte sedimentation rate, C-reactive protein, and urinalysis are routinely normal.

Erythema multiforme and urticarial vasculitis are part of the differential

The differential diagnosis in this case includes erythema multiforme, Henoch-Schönlein purpura, serum sickness-like reaction, and urticarial vasculitis (TABLE^1,2,4).

Continue to: Erythema multiforme

Erythema multiforme is a common misdiagnosis in patients with urticaria multiforme.^1,2 The erythema multiforme rash has a “target” lesion with outer erythema and central ecchymosis, which may develop blisters or necrosis. Lesions are fixed and last 2 to 3 weeks. Unlike urticaria multiforme, patients with erythema multiforme commonly have mucous membrane erosions and occasionally ulcerations. Facial and acral edema is rare. Treatment is largely symptomatic and can include glucocorticoids. Antiviral medications may be used to treat recurrences.^1,2

Henoch-Schönlein purpura is an immunoglobulin A–mediated vasculitis that affects the skin, gastrointestinal tract, and joints.^4,5 Patients often present with arthralgias, gastrointestinal symptoms such as abdominal pain and bleeding, and a nonpruritic, erythematous rash that progresses to palpable purpura in dependent areas of the body. Treatment is generally symptomatic, but steroids may be used in severe cases.^4,5

Serum sickness-like reaction can manifest with angioedema and a similar urticarial rash (with central clearing) that lasts 1 to 6 weeks.^1,2,6,7 However, patients tend to have a high-grade fever, arthralgias, myalgias, and lymphadenopathy while dermatographism is absent. Treatment includes discontinuing the offending agent and the use of H1 and H2 antihistamines and steroids, in severe cases.

Urticarial vasculitis manifests as plaques or wheals lasting 1 to 7 days that may cause burning and pain but not pruritis.^2,5 Purpura or hypopigmentation may develop as the hives resolve. Angioedema and arthralgias are common, but dermatographism is not present. Triggers include infections, autoimmune disease, malignancy, and the use of certain medications. H1 and H2 blockers and nonsteroidal anti-inflammatory agents are first-line therapy.²

Step 1: Discontinue offending agents; Step 2: Recommend antihistamines

Treatment consists of discontinuing any offending agent (if suspected) and using systemic H1 or H2 antihistamines for symptom relief. Systemic steroids should only be given in refractory cases.

Continue to: Our patient's amoxicillin

Our patient’s amoxicillin was discontinued, and he was started on a 14-day course of cetirizine 5 mg bid and hydroxyzine 10 mg at bedtime. He was also started on triamcinolone 0.1% cream to be applied twice daily for 1 week. During his 3-day hospital stay, his fever resolved and his rash and edema improved.

During an outpatient follow-up visit with a pediatric dermatologist 2 weeks after discharge, the patient’s rash was still present and dermatographism was noted. In light of this, his parents were instructed to continue giving the cetirizine and hydroxyzine once daily for an additional 2 weeks and to return as needed.

ON101 (Fespixon, Oneness Biotech), a first-in-class, macrophage-regulating, wound-healing cream for diabetic foot ulcers has shown benefit over absorbent dressings in a phase 3 trial, with another trial ongoing.

The product became available in Taiwan on July 4, 2021, after receiving regulatory approval from the Taiwan Food and Drug Administration based on efficacy and safety findings in a three-country phase 3 clinical trial.  

Oneness Biotech has also just started a second phase 3 trial in the United States, with a planned enrollment of 208 patients with diabetic foot ulcers, which will compare ON101 cream versus placebo cream, in addition to standard care, over 20 weeks.

The company expects to complete that trial and file a new drug application with the U.S. Food and Drug Administration in 2023, and a global launch is planned for 2025, said Oneness Biotech founder and CEO William Lu.
 

Current and upcoming trials

The Taiwan FDA approval of ON101 was based on a 236-patient clinical trial conducted in Taiwan, China, and the United States by Yu-Yao Huang MD, PhD, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, and colleagues, which was published online Sept. 3, 2021, in JAMA Network Open.

The study results will also be presented during an oral session at the European Association for the Study of Diabetes meeting on Sept. 30.

The published trial showed that foot ulcers treated with ON101 cream were almost three times more likely to be completely healed at 16 weeks than those treated with standard care with an absorbent dressing (Aquacel Hydrofiber, ConvaTec) (odds ratio, 2.84; P < .001).

“The findings of this study suggest that ON101, a macrophage regulator that behaves differently from moisture-retaining dressings, represents an active-healing alternative for home and primary care of patients with chronic [diabetic foot ulcers],” the researchers concluded.

“ON101 was also granted a fast track designation by the U.S. FDA in March this year,” senior author Shun-Chen Chang, MD, Taipei Medical University–Shuang Ho Hospital, New Taipei City, Taiwan, said in an interview.

“Patients in the United States can access this new drug via the expanded access program or by participating in the second phase 3 trial in the United States,” added coauthor Shawn M. Cazzell, DPM, chief medical officer, Limb Preservation Platform, Fresno, Calif., who is involved with both trials.

It is “exciting” to have a new therapy for diabetic foot ulcers, said Dr. Cazzell, because they are serious and life-threatening.
 

Could cream with plant extracts surpass current care?

Current standard clinical care for diabetic foot ulcer consists of debridement, off-loading, infection control, and maintaining a moist environment with dressings, Huang and colleagues explain. If the foot ulcer does not respond, growth factors, tissue-engineering products, hyperbaric oxygen, or negative pressure wound therapies may be used.

However, the number of amputations from chronic diabetic foot ulcers that do not heal is increasing, pointing to a need for better treatment options.  

Hyperglycemia increases the ratio of M1 proinflammatory macrophages to M2 proregenerative macrophages, and accumulating evidence suggests this might be a potential treatment target.  

Researchers at Oneness Biotech showed that ON101, which is comprised of extracts from two plants, Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages.

An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis.

In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model. This was followed by promising efficacy and safety results in two trials of 24 patients and 30 patients.
 

Significantly better healing with ON101 than standard care

For the current phase 3, randomized clinical trial, researchers enrolled patients in 21 clinics from November 2012 to May 2020.

To be eligible for the study, patients had to be 20-80 years old, with a hemoglobin A1c less than 12%. They also had to have a Wagner grade 1 or 2 foot ulcer that was 1-25 cm² after debridement, had been treated with standard care, and was present for at least 4 weeks.

Patients were a mean age of 57 years and 74% were men. They had a mean A1c of 8.1%, and 61% had had diabetes for more than 10 years.

Most (78%) of the diabetic foot ulcers were Wagner grade 2. The wounds had a mean area of 4.8 cm² and had been present for a mean of 7 months.

Patients were instructed on how to self-administer ON101 cream twice a day (treatment group, n = 122) or how to apply an absorbent dressing and change it daily or two or three times a week (standard care group, n = 114). All patients were allowed to apply a sterile gauze dressing.  

They visited the clinic every 2 weeks during the 16-week treatment phase and 12-week observation phase.

In the full analysis set, 74 patients (61%) in the ON101 group and 40 patients (35%) in the standard care group had complete wound healing after 16 weeks of treatment.

The subgroup of patients at higher risk of poor wound healing (A1c >9%, ulcer area >5 cm², and diabetic foot ulcer duration >6 months) also had significantly better healing with the ON101 cream than standard care.

There were seven (5.7%) treatment-emergent adverse events in the ON101 group versus five (4.4%) in the standard care group.

There were no treatment-related serious adverse events in the ON101 group versus one (0.9%) in the comparator group.

The study was funded by Oneness Biotech, Microbio Group, and Shanghai Haihe Pharmaceutical. One author has reported receiving fees from Oneness Biotech, and Dr. Chang has reported receiving a speakers fee from Oneness Biotech. The other authors reported no relevant financial relationships.

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

ON101 (Fespixon, Oneness Biotech), a first-in-class, macrophage-regulating, wound-healing cream for diabetic foot ulcers has shown benefit over absorbent dressings in a phase 3 trial, with another trial ongoing.

The product became available in Taiwan on July 4, 2021, after receiving regulatory approval from the Taiwan Food and Drug Administration based on efficacy and safety findings in a three-country phase 3 clinical trial.  

Oneness Biotech has also just started a second phase 3 trial in the United States, with a planned enrollment of 208 patients with diabetic foot ulcers, which will compare ON101 cream versus placebo cream, in addition to standard care, over 20 weeks.

The company expects to complete that trial and file a new drug application with the U.S. Food and Drug Administration in 2023, and a global launch is planned for 2025, said Oneness Biotech founder and CEO William Lu.
 

Current and upcoming trials

The Taiwan FDA approval of ON101 was based on a 236-patient clinical trial conducted in Taiwan, China, and the United States by Yu-Yao Huang MD, PhD, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, and colleagues, which was published online Sept. 3, 2021, in JAMA Network Open.

The study results will also be presented during an oral session at the European Association for the Study of Diabetes meeting on Sept. 30.

The published trial showed that foot ulcers treated with ON101 cream were almost three times more likely to be completely healed at 16 weeks than those treated with standard care with an absorbent dressing (Aquacel Hydrofiber, ConvaTec) (odds ratio, 2.84; P < .001).

“The findings of this study suggest that ON101, a macrophage regulator that behaves differently from moisture-retaining dressings, represents an active-healing alternative for home and primary care of patients with chronic [diabetic foot ulcers],” the researchers concluded.

“ON101 was also granted a fast track designation by the U.S. FDA in March this year,” senior author Shun-Chen Chang, MD, Taipei Medical University–Shuang Ho Hospital, New Taipei City, Taiwan, said in an interview.

“Patients in the United States can access this new drug via the expanded access program or by participating in the second phase 3 trial in the United States,” added coauthor Shawn M. Cazzell, DPM, chief medical officer, Limb Preservation Platform, Fresno, Calif., who is involved with both trials.

It is “exciting” to have a new therapy for diabetic foot ulcers, said Dr. Cazzell, because they are serious and life-threatening.
 

Could cream with plant extracts surpass current care?

Current standard clinical care for diabetic foot ulcer consists of debridement, off-loading, infection control, and maintaining a moist environment with dressings, Huang and colleagues explain. If the foot ulcer does not respond, growth factors, tissue-engineering products, hyperbaric oxygen, or negative pressure wound therapies may be used.

However, the number of amputations from chronic diabetic foot ulcers that do not heal is increasing, pointing to a need for better treatment options.  

Hyperglycemia increases the ratio of M1 proinflammatory macrophages to M2 proregenerative macrophages, and accumulating evidence suggests this might be a potential treatment target.  

Researchers at Oneness Biotech showed that ON101, which is comprised of extracts from two plants, Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages.

An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis.

In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model. This was followed by promising efficacy and safety results in two trials of 24 patients and 30 patients.
 

Significantly better healing with ON101 than standard care

For the current phase 3, randomized clinical trial, researchers enrolled patients in 21 clinics from November 2012 to May 2020.

To be eligible for the study, patients had to be 20-80 years old, with a hemoglobin A1c less than 12%. They also had to have a Wagner grade 1 or 2 foot ulcer that was 1-25 cm² after debridement, had been treated with standard care, and was present for at least 4 weeks.

Patients were a mean age of 57 years and 74% were men. They had a mean A1c of 8.1%, and 61% had had diabetes for more than 10 years.

Most (78%) of the diabetic foot ulcers were Wagner grade 2. The wounds had a mean area of 4.8 cm² and had been present for a mean of 7 months.

Patients were instructed on how to self-administer ON101 cream twice a day (treatment group, n = 122) or how to apply an absorbent dressing and change it daily or two or three times a week (standard care group, n = 114). All patients were allowed to apply a sterile gauze dressing.  

They visited the clinic every 2 weeks during the 16-week treatment phase and 12-week observation phase.

In the full analysis set, 74 patients (61%) in the ON101 group and 40 patients (35%) in the standard care group had complete wound healing after 16 weeks of treatment.

The subgroup of patients at higher risk of poor wound healing (A1c >9%, ulcer area >5 cm², and diabetic foot ulcer duration >6 months) also had significantly better healing with the ON101 cream than standard care.

There were seven (5.7%) treatment-emergent adverse events in the ON101 group versus five (4.4%) in the standard care group.

There were no treatment-related serious adverse events in the ON101 group versus one (0.9%) in the comparator group.

The study was funded by Oneness Biotech, Microbio Group, and Shanghai Haihe Pharmaceutical. One author has reported receiving fees from Oneness Biotech, and Dr. Chang has reported receiving a speakers fee from Oneness Biotech. The other authors reported no relevant financial relationships.

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

ON101 (Fespixon, Oneness Biotech), a first-in-class, macrophage-regulating, wound-healing cream for diabetic foot ulcers has shown benefit over absorbent dressings in a phase 3 trial, with another trial ongoing.

The product became available in Taiwan on July 4, 2021, after receiving regulatory approval from the Taiwan Food and Drug Administration based on efficacy and safety findings in a three-country phase 3 clinical trial.  

Oneness Biotech has also just started a second phase 3 trial in the United States, with a planned enrollment of 208 patients with diabetic foot ulcers, which will compare ON101 cream versus placebo cream, in addition to standard care, over 20 weeks.

The company expects to complete that trial and file a new drug application with the U.S. Food and Drug Administration in 2023, and a global launch is planned for 2025, said Oneness Biotech founder and CEO William Lu.
 

Current and upcoming trials

The Taiwan FDA approval of ON101 was based on a 236-patient clinical trial conducted in Taiwan, China, and the United States by Yu-Yao Huang MD, PhD, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, and colleagues, which was published online Sept. 3, 2021, in JAMA Network Open.

The study results will also be presented during an oral session at the European Association for the Study of Diabetes meeting on Sept. 30.

The published trial showed that foot ulcers treated with ON101 cream were almost three times more likely to be completely healed at 16 weeks than those treated with standard care with an absorbent dressing (Aquacel Hydrofiber, ConvaTec) (odds ratio, 2.84; P < .001).

“The findings of this study suggest that ON101, a macrophage regulator that behaves differently from moisture-retaining dressings, represents an active-healing alternative for home and primary care of patients with chronic [diabetic foot ulcers],” the researchers concluded.

“ON101 was also granted a fast track designation by the U.S. FDA in March this year,” senior author Shun-Chen Chang, MD, Taipei Medical University–Shuang Ho Hospital, New Taipei City, Taiwan, said in an interview.

“Patients in the United States can access this new drug via the expanded access program or by participating in the second phase 3 trial in the United States,” added coauthor Shawn M. Cazzell, DPM, chief medical officer, Limb Preservation Platform, Fresno, Calif., who is involved with both trials.

It is “exciting” to have a new therapy for diabetic foot ulcers, said Dr. Cazzell, because they are serious and life-threatening.
 

Could cream with plant extracts surpass current care?

Current standard clinical care for diabetic foot ulcer consists of debridement, off-loading, infection control, and maintaining a moist environment with dressings, Huang and colleagues explain. If the foot ulcer does not respond, growth factors, tissue-engineering products, hyperbaric oxygen, or negative pressure wound therapies may be used.

However, the number of amputations from chronic diabetic foot ulcers that do not heal is increasing, pointing to a need for better treatment options.  

Hyperglycemia increases the ratio of M1 proinflammatory macrophages to M2 proregenerative macrophages, and accumulating evidence suggests this might be a potential treatment target.  

Researchers at Oneness Biotech showed that ON101, which is comprised of extracts from two plants, Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages.

An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis.

In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model. This was followed by promising efficacy and safety results in two trials of 24 patients and 30 patients.
 

Significantly better healing with ON101 than standard care

For the current phase 3, randomized clinical trial, researchers enrolled patients in 21 clinics from November 2012 to May 2020.

To be eligible for the study, patients had to be 20-80 years old, with a hemoglobin A1c less than 12%. They also had to have a Wagner grade 1 or 2 foot ulcer that was 1-25 cm² after debridement, had been treated with standard care, and was present for at least 4 weeks.

Patients were a mean age of 57 years and 74% were men. They had a mean A1c of 8.1%, and 61% had had diabetes for more than 10 years.

Most (78%) of the diabetic foot ulcers were Wagner grade 2. The wounds had a mean area of 4.8 cm² and had been present for a mean of 7 months.

Patients were instructed on how to self-administer ON101 cream twice a day (treatment group, n = 122) or how to apply an absorbent dressing and change it daily or two or three times a week (standard care group, n = 114). All patients were allowed to apply a sterile gauze dressing.  

They visited the clinic every 2 weeks during the 16-week treatment phase and 12-week observation phase.

In the full analysis set, 74 patients (61%) in the ON101 group and 40 patients (35%) in the standard care group had complete wound healing after 16 weeks of treatment.

The subgroup of patients at higher risk of poor wound healing (A1c >9%, ulcer area >5 cm², and diabetic foot ulcer duration >6 months) also had significantly better healing with the ON101 cream than standard care.

There were seven (5.7%) treatment-emergent adverse events in the ON101 group versus five (4.4%) in the standard care group.

There were no treatment-related serious adverse events in the ON101 group versus one (0.9%) in the comparator group.

The study was funded by Oneness Biotech, Microbio Group, and Shanghai Haihe Pharmaceutical. One author has reported receiving fees from Oneness Biotech, and Dr. Chang has reported receiving a speakers fee from Oneness Biotech. The other authors reported no relevant financial relationships.

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

An expert panel of 48 dermatologists from 13 countries has developed recommendations to guide efforts aimed at preventing cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients.

The recommendations were published online on Sept. 1 in JAMA Dermatology.

Because of lifelong immunosuppression, solid organ transplant recipients (SOTRs) have a risk of CSCC that is 20-200 times higher than in the general population and despite a growing literature on prevention of CSCC in these patients, uncertainty remains regarding best practices for various patient scenarios.

Paul Massey, MD, MPH, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.

The survey design was guided by a novel actinic damage and skin cancer index (AD-SCI) made up of six ordinal stages corresponding to an increasing burden of actinic damage and CSCC.

The AD-SCI stage-based recommendations were established when consensus was reached (80% or higher concordance) or near consensus was reached (70%-80% concordance) among panel members.

For five of the six AD-SCI stages, the panel was able to make recommendations. Key recommendations include:
 

• Cryotherapy for scattered AK.
• Field therapy for AK when grouped in one site, unless AKs are thick, in which case field therapy and cryotherapy are recommended.
• Combination lesion-directed and field therapy with fluorouracil for field cancerized skin.
• Initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple CSCCs at a high rate (10 per year) or develop high-risk CSCC (defined by a tumor with roughly ≥20% risk of nodal metastasis). The panel did not make a recommendation as to the best immunosuppression modification strategy to pursue.

Lingering questions

The panel was unable to reach consensus on a recommendation for SOTRs with a first low-risk CSCC, reflecting “clinical equipoise” in this situation and the need for further study in this clinical scenario, they say.

The panel did not make a recommendation for use of nicotinamide or capecitabine in any of the six stages, which is “notable,” they acknowledge, given results of a double-blind randomized controlled trial in immunocompetent patients demonstrating benefit in preventing AKs and CSCCs, as reported previously.

Nearly three-quarters of the panel felt that a lack of efficacy data specifically for the SOTR population limited their use of nicotinamide. “Given the low cost, high safety, and demonstration of CSCC reduction in non-SOTRs, nicotinamide administration may be an area for further consideration and expanded study,” the panel wrote.

As for capecitabine, the panel notes that case series in SOTRs have found efficacy for chemoprevention, but randomized controlled studies are lacking. More than half of the panel noted that they did not have routine access to capecitabine in their practice.

The panel recommended routine skin surveillance and sunscreen use for all patients.

“These recommendations reflect consensus among expert transplant dermatologists and the incorporation of limited and sometimes contradictory evidence into real-world clinical experience across a range of CSCC disease severity,” the panel said.

“Areas of consensus may aid physicians in establishing best practices regarding prevention of CSCC in SOTRs in the setting of limited high level of evidence data in this population,” they added.

This research had no specific funding. Author disclosures included serving as a consultant to Regeneron, Sanofi, and receiving research funding from Castle Biosciences, Regeneron, Novartis, and Genentech. A complete list of disclosures for panel members is available with the original article.

An expert panel of 48 dermatologists from 13 countries has developed recommendations to guide efforts aimed at preventing cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients.

The recommendations were published online on Sept. 1 in JAMA Dermatology.

Because of lifelong immunosuppression, solid organ transplant recipients (SOTRs) have a risk of CSCC that is 20-200 times higher than in the general population and despite a growing literature on prevention of CSCC in these patients, uncertainty remains regarding best practices for various patient scenarios.

Paul Massey, MD, MPH, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.

The survey design was guided by a novel actinic damage and skin cancer index (AD-SCI) made up of six ordinal stages corresponding to an increasing burden of actinic damage and CSCC.

The AD-SCI stage-based recommendations were established when consensus was reached (80% or higher concordance) or near consensus was reached (70%-80% concordance) among panel members.

For five of the six AD-SCI stages, the panel was able to make recommendations. Key recommendations include:
 

• Cryotherapy for scattered AK.
• Field therapy for AK when grouped in one site, unless AKs are thick, in which case field therapy and cryotherapy are recommended.
• Combination lesion-directed and field therapy with fluorouracil for field cancerized skin.
• Initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple CSCCs at a high rate (10 per year) or develop high-risk CSCC (defined by a tumor with roughly ≥20% risk of nodal metastasis). The panel did not make a recommendation as to the best immunosuppression modification strategy to pursue.

Lingering questions

The panel was unable to reach consensus on a recommendation for SOTRs with a first low-risk CSCC, reflecting “clinical equipoise” in this situation and the need for further study in this clinical scenario, they say.

The panel did not make a recommendation for use of nicotinamide or capecitabine in any of the six stages, which is “notable,” they acknowledge, given results of a double-blind randomized controlled trial in immunocompetent patients demonstrating benefit in preventing AKs and CSCCs, as reported previously.

Nearly three-quarters of the panel felt that a lack of efficacy data specifically for the SOTR population limited their use of nicotinamide. “Given the low cost, high safety, and demonstration of CSCC reduction in non-SOTRs, nicotinamide administration may be an area for further consideration and expanded study,” the panel wrote.

As for capecitabine, the panel notes that case series in SOTRs have found efficacy for chemoprevention, but randomized controlled studies are lacking. More than half of the panel noted that they did not have routine access to capecitabine in their practice.

The panel recommended routine skin surveillance and sunscreen use for all patients.

“These recommendations reflect consensus among expert transplant dermatologists and the incorporation of limited and sometimes contradictory evidence into real-world clinical experience across a range of CSCC disease severity,” the panel said.

“Areas of consensus may aid physicians in establishing best practices regarding prevention of CSCC in SOTRs in the setting of limited high level of evidence data in this population,” they added.

This research had no specific funding. Author disclosures included serving as a consultant to Regeneron, Sanofi, and receiving research funding from Castle Biosciences, Regeneron, Novartis, and Genentech. A complete list of disclosures for panel members is available with the original article.

An expert panel of 48 dermatologists from 13 countries has developed recommendations to guide efforts aimed at preventing cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients.

The recommendations were published online on Sept. 1 in JAMA Dermatology.

Because of lifelong immunosuppression, solid organ transplant recipients (SOTRs) have a risk of CSCC that is 20-200 times higher than in the general population and despite a growing literature on prevention of CSCC in these patients, uncertainty remains regarding best practices for various patient scenarios.

Paul Massey, MD, MPH, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.

The survey design was guided by a novel actinic damage and skin cancer index (AD-SCI) made up of six ordinal stages corresponding to an increasing burden of actinic damage and CSCC.

The AD-SCI stage-based recommendations were established when consensus was reached (80% or higher concordance) or near consensus was reached (70%-80% concordance) among panel members.

For five of the six AD-SCI stages, the panel was able to make recommendations. Key recommendations include:
 

• Cryotherapy for scattered AK.
• Field therapy for AK when grouped in one site, unless AKs are thick, in which case field therapy and cryotherapy are recommended.
• Combination lesion-directed and field therapy with fluorouracil for field cancerized skin.
• Initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple CSCCs at a high rate (10 per year) or develop high-risk CSCC (defined by a tumor with roughly ≥20% risk of nodal metastasis). The panel did not make a recommendation as to the best immunosuppression modification strategy to pursue.

Lingering questions

The panel was unable to reach consensus on a recommendation for SOTRs with a first low-risk CSCC, reflecting “clinical equipoise” in this situation and the need for further study in this clinical scenario, they say.

The panel did not make a recommendation for use of nicotinamide or capecitabine in any of the six stages, which is “notable,” they acknowledge, given results of a double-blind randomized controlled trial in immunocompetent patients demonstrating benefit in preventing AKs and CSCCs, as reported previously.

Nearly three-quarters of the panel felt that a lack of efficacy data specifically for the SOTR population limited their use of nicotinamide. “Given the low cost, high safety, and demonstration of CSCC reduction in non-SOTRs, nicotinamide administration may be an area for further consideration and expanded study,” the panel wrote.

As for capecitabine, the panel notes that case series in SOTRs have found efficacy for chemoprevention, but randomized controlled studies are lacking. More than half of the panel noted that they did not have routine access to capecitabine in their practice.

The panel recommended routine skin surveillance and sunscreen use for all patients.

“These recommendations reflect consensus among expert transplant dermatologists and the incorporation of limited and sometimes contradictory evidence into real-world clinical experience across a range of CSCC disease severity,” the panel said.

“Areas of consensus may aid physicians in establishing best practices regarding prevention of CSCC in SOTRs in the setting of limited high level of evidence data in this population,” they added.

This research had no specific funding. Author disclosures included serving as a consultant to Regeneron, Sanofi, and receiving research funding from Castle Biosciences, Regeneron, Novartis, and Genentech. A complete list of disclosures for panel members is available with the original article.