Psoriasis

In November 2019, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released their first set of recommendations for the management of pediatric psoriasis.¹ The pediatric guidelines discuss methods of quantifying disease severity in children, triggers and comorbidities, and the efficacy and safety of various therapeutic agents. This review aims to discuss, in a condensed form, special considerations unique to the management of children with psoriasis as presented in the guidelines as well as grade A– and grade B–level treatment recommendations (Table).

Quantifying Psoriasis Severity in Children

Percentage body surface area (BSA) involvement is the most common mode of grading psoriasis severity, with less than 3% BSA involvement being considered mild, 3% to 10% BSA moderate, and more than 10% severe disease. In children, the standard method of measuring BSA is the rule of 9’s: the head and each arm make up 9% of the total BSA, each leg and the front and back of the torso respectively each make up 18%, and the genitalia make up 1%. It also is important to consider impact on quality of life, which may be remarkable in spite of limited BSA involvement. The children’s dermatology life quality index score may be utilized in combination with affected BSA to determine the burden of psoriasis in context of impact on daily life. This metric is available in both written and cartoon form, and it consists of 10 questions that include variables such as severity of itch, impact on social life, and effects on sleep. Most notably, this tool incorporates pruritus,² which generally is addressed inadequately in pediatric psoriasis.

Triggers and Comorbidities in Pediatric Patients

In children, it is important to identify and eliminate modifiable factors that may prompt psoriasis flares. Infections, particularly group A beta-hemolytic streptococcal infections, are a major trigger in neonates and infants. Other exacerbating factors in children include emotional stress, secondhand cigarette smoke, Kawasaki disease, and withdrawal from systemic corticosteroids.

Psoriatic arthritis (PsA) is a burdensome comorbidity affecting children with psoriasis. The prevalence of joint disease is 15-times greater in children with psoriasis vs those without,³ and 80% of children with PsA develop rheumatologic symptoms, which typically include oligoarticular disease and dactylitis in infants and girls and enthesitis and axial joint involvement in boys and older children, years prior to the onset of cutaneous disease.⁴ Uveitis often occurs in children with psoriasis and PsA but not in those with isolated cutaneous disease.

Compared to unaffected children, pediatric patients with psoriasis have greater prevalence of metabolic and cardiovascular risk factors during childhood, including central obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, atherosclerosis, arrythmia, and valvular heart disease. Family history of obesity increases the risk for early-onset development of cutaneous lesions,^5,6 and weight reduction may alleviate severity of psoriasis lesions.⁷ In the United States, many of the metabolic associations observed are particularly robust in Black and Hispanic children vs those of other races. Furthermore, the prevalence of inflammatory bowel disease is 3- to 4-times higher in children with psoriasis compared to those without.

As with other cutaneous diseases, it is important to be aware of social and mental health concerns in children with psoriasis. The majority of pediatric patients with psoriasis experience name-calling, shaming, or bullying, and many have concerns from skin shedding and malodor. Independent risk for depression after the onset of psoriasis is high. Affected older children and adolescents are at increased risk for alcohol and drug abuse as well as eating disorders.

Despite these identified comorbidities, there are no unique screening recommendations for arthritis, ophthalmologic disease, metabolic disease, cardiovascular disease, gastrointestinal tract disease, or mental health issues in children with psoriasis. Rather, these patients should be monitored according to the American Academy of Pediatrics or American Diabetes Association guidelines for all pediatric patients.^8,9 Nonetheless, educating patients and guardians about these potential issues may be warranted.

Topical Therapies

For children with mild to moderate psoriasis, topical therapies are first line. Despite being off label, topical corticosteroids are the mainstay of therapy for localized psoriatic plaques in children. Topical vitamin D analogues—calcitriol and calcipotriol/calcipotriene—are highly effective and well tolerated, and they frequently are used in combination with topical corticosteroids. Topical calcineurin inhibitors, namely tacrolimus, also are used off label but are considered first line for sensitive regions of the skin in children, including the face, genitalia, and body folds. There currently is limited evidence for supporting the use of the topical vitamin A analogue tazarotene in children with psoriasis, though some consider its off-label use effective for pediatric nail psoriasis. It also may be used as an adjunct to topical corticosteroids to minimize irritation.

Although there is no gold standard topical regimen, combination therapy with a high-potency topical steroid and topical vitamin D analogue commonly is used to minimize steroid-induced side effects. For the first 2 weeks of treatment, they each may be applied once daily or mixed together and applied twice daily. For subsequent maintenance, topical calcipotriene may be applied on weekdays and topical steroids only on weekends. Combination calcipotriol–betamethasone dipropionate also is available as cream, ointment, foam, and suspension vehicles for use on the body and scalp in children aged 12 years and older. Tacrolimus ointment 0.1% may be applied in a thin layer up to twice daily. Concurrent emollient use also is recommended with these therapies.

Health care providers should educate patients and guardians about the potential side effects of topical therapies. They also should provide explicit instructions for amount, site, frequency, and duration of application. Topical corticosteroids commonly result in burning on application and may potentially cause skin thinning and striae with overuse. Topical vitamin D analogues may result in local irritation that may be improved by concurrent emollient use, and they generally should be avoided on sensitive sites. Topical calcineurin inhibitors are associated with burning, stinging, and pruritus, and the US Food and Drug Administration has issued a black-box warning related to risk for lymphoma with their chronic intermittent use. However, it was based on rare reports of lymphoma in transplant patients taking oral calcineurin inhibitors; no clinical trials to date in humans have demonstrated an increased risk for malignancy with topical calcineurin inhibitors.¹⁰ Tazarotene should be used cautiously in females of childbearing age given its teratogenic potential.

Children younger than 7 years are especially prone to suppression of the hypothalamic-pituitary-adrenal axis from topical corticosteroid therapy and theoretically hypercalcemia and hypervitaminosis D from topical vitamin D analogues, as their high BSA-to-volume ratio increases potential for systemic absorption. Children should avoid occlusive application of topical vitamin D analogues to large areas of the skin. Monitoring of vitamin D metabolites in the serum may be considered if calcipotriene or calcipotriol application to a large BSA is warranted.

Light-Based Therapy

In children with widespread psoriasis or those refractory to topical therapy, phototherapy may be considered. Narrowband UVB (311- to 313-nm wavelength) therapy is considered a first-line form of phototherapy in pediatric psoriasis. Mineral oil or emollient pretreatment to affected areas may augment the efficacy of UV-based treatments.¹¹ Excimer laser and UVA also may be efficacious, though evidence is limited in children. Treatment is recommended to start at 3 days a week, and once improvement is seen, the frequency can be decreased to 2 days a week. Once desired clearance is achieved, maintenance therapy can be continued at even longer intervals. Adjunctive use of tar preparations may potentiate the efficacy of phototherapy, though there is a theoretical increased risk for carcinogenicity with prolonged use of coal tar. Side effects of phototherapy include erythema, blistering hyperpigmentation, and pruritus. Psoralen is contraindicated in children younger than 12 years. All forms of phototherapy are contraindicated in children with generalized erythroderma and cutaneous cancer syndromes. Other important pediatric-specific considerations include anxiety that may be provoked by UV light machines and inconvenience of frequent appointments.

Nonbiologic Systemic Therapies

Systemic therapies may be considered in children with recalcitrant, widespread, or rapidly progressing psoriasis, particularly if the disease is accompanied by severe emotional and psychological burden. These drugs, which include methotrexate, cyclosporine, and acitretin (see eTable for recommended dosing), are advantageous in that they may be combined with other therapies; however, they have potential for dangerous toxicities.

Methotrexate is the most frequently utilized systemic therapy for psoriasis worldwide in children because of its low cost, once-weekly dosing, and the substantial amount of long-term efficacy and safety data available in the pediatric population. It is slow acting initially but has excellent long-term efficacy for nearly every subtype of psoriasis. The most common side effect of methotrexate is gastrointestinal tract intolerance. Nonetheless, adverse events are rare in children without prior history, with 1 large study (N=289) reporting no adverse events in more than 90% of patients aged 9 to 14 years treated with methotrexate.¹² Current guidelines recommend monitoring for bone marrow suppression and elevated transaminase levels 4 to 6 days after initiating treatment.¹ The absolute contraindications for methotrexate are pregnancy and liver disease, and caution should be taken in children with metabolic risk factors. Adolescents must be counseled regarding the elevated risk for hepatotoxicity associated with alcohol ingestion. Methotrexate therapy also requires 1 mg folic acid supplementation 6 to 7 days a week, which decreases the risk for developing folic acid deficiency and may decrease gastrointestinal tract intolerance and hepatic side effects that may result from therapy.

Cyclosporine is an effective and well-tolerated option for rapid control of severe psoriasis in children. It is useful for various types of psoriasis but generally is reserved for more severe subtypes, such as generalized pustular psoriasis, erythrodermic psoriasis, and uncontrolled plaque psoriasis. Long-term use of cyclosporine may result in renal toxicity and hypertension, and this therapy is absolutely contraindicated in children with kidney disease or hypertension at baseline. It is strongly recommended to evaluate blood pressure every week for the first month of therapy and at every subsequent follow-up visit, which may occur at variable intervals based on the judgement of the provider. Evaluation before and during treatment with cyclosporine also should include a complete blood cell count, complete metabolic panel, and lipid panel.

Systemic retinoids have a unique advantage over methotrexate and cyclosporine in that they are not immunosuppressive and therefore are not contraindicated in children who are very young or immunosuppressed. Children receiving systemic retinoids also can receive routine live vaccines—measles-mumps-rubella, varicella zoster, and rotavirus—that are contraindicated with other systemic therapies. Acitretin is particularly effective in pediatric patients with diffuse guttate psoriasis, pustular psoriasis, and palmoplantar psoriasis. Narrowband UVB therapy has been shown to augment the effectiveness of acitretin in children, which may allow for reduced acitretin dosing. Pustular psoriasis may respond as quickly as 3 weeks after initiation, whereas it may take 2 to 3 months before improvement is noticed in plaque psoriasis. Side effects of retinoids include skin dryness, hyperlipidemia, and gastrointestinal tract upset. The most severe long-term concern is skeletal toxicity, including premature epiphyseal closure, hyperostosis, periosteal bone formation, and decreased bone mineral density.¹ Vitamin A derivatives also are known teratogens and should be avoided in females of childbearing potential. Lipids and transaminases should be monitored routinely, and screening for depression and psychiatric symptoms should be performed frequently.¹

When utilizing systemic therapies, the objective should be to control the disease, maintain stability, and ultimately taper to the lowest effective dose or transition to a topical therapy, if feasible. Although no particular systemic therapy is recommended as first line for children with psoriasis, it is important to consider comorbidities, contraindications, monitoring frequency, mode of administration (injectable therapies elicit more psychological trauma in children than oral therapies), and expense when determining the best choice.

Biologics

Biologic agents are associated with very high to total psoriatic plaque clearance rates and require infrequent dosing and monitoring. However, their use may be limited by cost and injection phobias in children as well as limited evidence for their efficacy and safety in pediatric psoriasis. Several studies have established the safety and effectiveness of biologics in children with plaque psoriasis (see eTable for recommended dosing), whereas the evidence supporting their use in treating pustular and erythrodermic variants are limited to case reports and case series. The tumor necrosis factor α (TNF-α) inhibitor etanercept has been approved for use in children aged 4 years and older, and the IL-12/IL-23 inhibitor ustekinumab is approved in children aged 6 years and older. Other TNF-α inhibitors, namely infliximab and adalimumab, commonly are utilized off label for pediatric psoriasis. The most common side effect of biologic therapies in pediatric patients is injection-site reactions.¹ Prior to initiating therapy, children must undergo tuberculosis screening either by purified protein derivative testing or IFN-γ release assay. Testing should be repeated annually in individuals taking TNF-α inhibitors, though the utility of repeat testing when taking biologics in other classes is not clear. High-risk patients also should be screened for human immunodeficiency virus and hepatitis. Follow-up frequency may range from every 3 months to annually, based on judgement of the provider. In children who develop loss of response to biologics, methotrexate can be added to the regimen to attenuate formation of efficacy-reducing antidrug antibodies.

Final Thoughts

When managing children with psoriasis, it is important for dermatologists to appropriately educate guardians and children on the disease course, as well as consider the psychological, emotional, social, and financial factors that may direct decision-making regarding optimal therapeutics. Dermatologists should consider collaboration with the child’s primary care physician and other specialists to ensure that all needs are met.

These guidelines provide a framework agreed upon by numerous experts in pediatric psoriasis, but they are limited by gaps in the research. There still is much to be learned regarding the pathophysiology of psoriasis; the risk for developing comorbidities during adulthood; and the efficacy and safety of certain therapeutics, particularly biologics, in pediatric patients with psoriasis.

In November 2019, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released their first set of recommendations for the management of pediatric psoriasis.¹ The pediatric guidelines discuss methods of quantifying disease severity in children, triggers and comorbidities, and the efficacy and safety of various therapeutic agents. This review aims to discuss, in a condensed form, special considerations unique to the management of children with psoriasis as presented in the guidelines as well as grade A– and grade B–level treatment recommendations (Table).

Quantifying Psoriasis Severity in Children

Percentage body surface area (BSA) involvement is the most common mode of grading psoriasis severity, with less than 3% BSA involvement being considered mild, 3% to 10% BSA moderate, and more than 10% severe disease. In children, the standard method of measuring BSA is the rule of 9’s: the head and each arm make up 9% of the total BSA, each leg and the front and back of the torso respectively each make up 18%, and the genitalia make up 1%. It also is important to consider impact on quality of life, which may be remarkable in spite of limited BSA involvement. The children’s dermatology life quality index score may be utilized in combination with affected BSA to determine the burden of psoriasis in context of impact on daily life. This metric is available in both written and cartoon form, and it consists of 10 questions that include variables such as severity of itch, impact on social life, and effects on sleep. Most notably, this tool incorporates pruritus,² which generally is addressed inadequately in pediatric psoriasis.

Triggers and Comorbidities in Pediatric Patients

In children, it is important to identify and eliminate modifiable factors that may prompt psoriasis flares. Infections, particularly group A beta-hemolytic streptococcal infections, are a major trigger in neonates and infants. Other exacerbating factors in children include emotional stress, secondhand cigarette smoke, Kawasaki disease, and withdrawal from systemic corticosteroids.

Psoriatic arthritis (PsA) is a burdensome comorbidity affecting children with psoriasis. The prevalence of joint disease is 15-times greater in children with psoriasis vs those without,³ and 80% of children with PsA develop rheumatologic symptoms, which typically include oligoarticular disease and dactylitis in infants and girls and enthesitis and axial joint involvement in boys and older children, years prior to the onset of cutaneous disease.⁴ Uveitis often occurs in children with psoriasis and PsA but not in those with isolated cutaneous disease.

Compared to unaffected children, pediatric patients with psoriasis have greater prevalence of metabolic and cardiovascular risk factors during childhood, including central obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, atherosclerosis, arrythmia, and valvular heart disease. Family history of obesity increases the risk for early-onset development of cutaneous lesions,^5,6 and weight reduction may alleviate severity of psoriasis lesions.⁷ In the United States, many of the metabolic associations observed are particularly robust in Black and Hispanic children vs those of other races. Furthermore, the prevalence of inflammatory bowel disease is 3- to 4-times higher in children with psoriasis compared to those without.

As with other cutaneous diseases, it is important to be aware of social and mental health concerns in children with psoriasis. The majority of pediatric patients with psoriasis experience name-calling, shaming, or bullying, and many have concerns from skin shedding and malodor. Independent risk for depression after the onset of psoriasis is high. Affected older children and adolescents are at increased risk for alcohol and drug abuse as well as eating disorders.

Despite these identified comorbidities, there are no unique screening recommendations for arthritis, ophthalmologic disease, metabolic disease, cardiovascular disease, gastrointestinal tract disease, or mental health issues in children with psoriasis. Rather, these patients should be monitored according to the American Academy of Pediatrics or American Diabetes Association guidelines for all pediatric patients.^8,9 Nonetheless, educating patients and guardians about these potential issues may be warranted.

Topical Therapies

For children with mild to moderate psoriasis, topical therapies are first line. Despite being off label, topical corticosteroids are the mainstay of therapy for localized psoriatic plaques in children. Topical vitamin D analogues—calcitriol and calcipotriol/calcipotriene—are highly effective and well tolerated, and they frequently are used in combination with topical corticosteroids. Topical calcineurin inhibitors, namely tacrolimus, also are used off label but are considered first line for sensitive regions of the skin in children, including the face, genitalia, and body folds. There currently is limited evidence for supporting the use of the topical vitamin A analogue tazarotene in children with psoriasis, though some consider its off-label use effective for pediatric nail psoriasis. It also may be used as an adjunct to topical corticosteroids to minimize irritation.

Although there is no gold standard topical regimen, combination therapy with a high-potency topical steroid and topical vitamin D analogue commonly is used to minimize steroid-induced side effects. For the first 2 weeks of treatment, they each may be applied once daily or mixed together and applied twice daily. For subsequent maintenance, topical calcipotriene may be applied on weekdays and topical steroids only on weekends. Combination calcipotriol–betamethasone dipropionate also is available as cream, ointment, foam, and suspension vehicles for use on the body and scalp in children aged 12 years and older. Tacrolimus ointment 0.1% may be applied in a thin layer up to twice daily. Concurrent emollient use also is recommended with these therapies.

Health care providers should educate patients and guardians about the potential side effects of topical therapies. They also should provide explicit instructions for amount, site, frequency, and duration of application. Topical corticosteroids commonly result in burning on application and may potentially cause skin thinning and striae with overuse. Topical vitamin D analogues may result in local irritation that may be improved by concurrent emollient use, and they generally should be avoided on sensitive sites. Topical calcineurin inhibitors are associated with burning, stinging, and pruritus, and the US Food and Drug Administration has issued a black-box warning related to risk for lymphoma with their chronic intermittent use. However, it was based on rare reports of lymphoma in transplant patients taking oral calcineurin inhibitors; no clinical trials to date in humans have demonstrated an increased risk for malignancy with topical calcineurin inhibitors.¹⁰ Tazarotene should be used cautiously in females of childbearing age given its teratogenic potential.

Children younger than 7 years are especially prone to suppression of the hypothalamic-pituitary-adrenal axis from topical corticosteroid therapy and theoretically hypercalcemia and hypervitaminosis D from topical vitamin D analogues, as their high BSA-to-volume ratio increases potential for systemic absorption. Children should avoid occlusive application of topical vitamin D analogues to large areas of the skin. Monitoring of vitamin D metabolites in the serum may be considered if calcipotriene or calcipotriol application to a large BSA is warranted.

Light-Based Therapy

In children with widespread psoriasis or those refractory to topical therapy, phototherapy may be considered. Narrowband UVB (311- to 313-nm wavelength) therapy is considered a first-line form of phototherapy in pediatric psoriasis. Mineral oil or emollient pretreatment to affected areas may augment the efficacy of UV-based treatments.¹¹ Excimer laser and UVA also may be efficacious, though evidence is limited in children. Treatment is recommended to start at 3 days a week, and once improvement is seen, the frequency can be decreased to 2 days a week. Once desired clearance is achieved, maintenance therapy can be continued at even longer intervals. Adjunctive use of tar preparations may potentiate the efficacy of phototherapy, though there is a theoretical increased risk for carcinogenicity with prolonged use of coal tar. Side effects of phototherapy include erythema, blistering hyperpigmentation, and pruritus. Psoralen is contraindicated in children younger than 12 years. All forms of phototherapy are contraindicated in children with generalized erythroderma and cutaneous cancer syndromes. Other important pediatric-specific considerations include anxiety that may be provoked by UV light machines and inconvenience of frequent appointments.

Nonbiologic Systemic Therapies

Systemic therapies may be considered in children with recalcitrant, widespread, or rapidly progressing psoriasis, particularly if the disease is accompanied by severe emotional and psychological burden. These drugs, which include methotrexate, cyclosporine, and acitretin (see eTable for recommended dosing), are advantageous in that they may be combined with other therapies; however, they have potential for dangerous toxicities.

Methotrexate is the most frequently utilized systemic therapy for psoriasis worldwide in children because of its low cost, once-weekly dosing, and the substantial amount of long-term efficacy and safety data available in the pediatric population. It is slow acting initially but has excellent long-term efficacy for nearly every subtype of psoriasis. The most common side effect of methotrexate is gastrointestinal tract intolerance. Nonetheless, adverse events are rare in children without prior history, with 1 large study (N=289) reporting no adverse events in more than 90% of patients aged 9 to 14 years treated with methotrexate.¹² Current guidelines recommend monitoring for bone marrow suppression and elevated transaminase levels 4 to 6 days after initiating treatment.¹ The absolute contraindications for methotrexate are pregnancy and liver disease, and caution should be taken in children with metabolic risk factors. Adolescents must be counseled regarding the elevated risk for hepatotoxicity associated with alcohol ingestion. Methotrexate therapy also requires 1 mg folic acid supplementation 6 to 7 days a week, which decreases the risk for developing folic acid deficiency and may decrease gastrointestinal tract intolerance and hepatic side effects that may result from therapy.

Cyclosporine is an effective and well-tolerated option for rapid control of severe psoriasis in children. It is useful for various types of psoriasis but generally is reserved for more severe subtypes, such as generalized pustular psoriasis, erythrodermic psoriasis, and uncontrolled plaque psoriasis. Long-term use of cyclosporine may result in renal toxicity and hypertension, and this therapy is absolutely contraindicated in children with kidney disease or hypertension at baseline. It is strongly recommended to evaluate blood pressure every week for the first month of therapy and at every subsequent follow-up visit, which may occur at variable intervals based on the judgement of the provider. Evaluation before and during treatment with cyclosporine also should include a complete blood cell count, complete metabolic panel, and lipid panel.

Systemic retinoids have a unique advantage over methotrexate and cyclosporine in that they are not immunosuppressive and therefore are not contraindicated in children who are very young or immunosuppressed. Children receiving systemic retinoids also can receive routine live vaccines—measles-mumps-rubella, varicella zoster, and rotavirus—that are contraindicated with other systemic therapies. Acitretin is particularly effective in pediatric patients with diffuse guttate psoriasis, pustular psoriasis, and palmoplantar psoriasis. Narrowband UVB therapy has been shown to augment the effectiveness of acitretin in children, which may allow for reduced acitretin dosing. Pustular psoriasis may respond as quickly as 3 weeks after initiation, whereas it may take 2 to 3 months before improvement is noticed in plaque psoriasis. Side effects of retinoids include skin dryness, hyperlipidemia, and gastrointestinal tract upset. The most severe long-term concern is skeletal toxicity, including premature epiphyseal closure, hyperostosis, periosteal bone formation, and decreased bone mineral density.¹ Vitamin A derivatives also are known teratogens and should be avoided in females of childbearing potential. Lipids and transaminases should be monitored routinely, and screening for depression and psychiatric symptoms should be performed frequently.¹

When utilizing systemic therapies, the objective should be to control the disease, maintain stability, and ultimately taper to the lowest effective dose or transition to a topical therapy, if feasible. Although no particular systemic therapy is recommended as first line for children with psoriasis, it is important to consider comorbidities, contraindications, monitoring frequency, mode of administration (injectable therapies elicit more psychological trauma in children than oral therapies), and expense when determining the best choice.

Biologics

Biologic agents are associated with very high to total psoriatic plaque clearance rates and require infrequent dosing and monitoring. However, their use may be limited by cost and injection phobias in children as well as limited evidence for their efficacy and safety in pediatric psoriasis. Several studies have established the safety and effectiveness of biologics in children with plaque psoriasis (see eTable for recommended dosing), whereas the evidence supporting their use in treating pustular and erythrodermic variants are limited to case reports and case series. The tumor necrosis factor α (TNF-α) inhibitor etanercept has been approved for use in children aged 4 years and older, and the IL-12/IL-23 inhibitor ustekinumab is approved in children aged 6 years and older. Other TNF-α inhibitors, namely infliximab and adalimumab, commonly are utilized off label for pediatric psoriasis. The most common side effect of biologic therapies in pediatric patients is injection-site reactions.¹ Prior to initiating therapy, children must undergo tuberculosis screening either by purified protein derivative testing or IFN-γ release assay. Testing should be repeated annually in individuals taking TNF-α inhibitors, though the utility of repeat testing when taking biologics in other classes is not clear. High-risk patients also should be screened for human immunodeficiency virus and hepatitis. Follow-up frequency may range from every 3 months to annually, based on judgement of the provider. In children who develop loss of response to biologics, methotrexate can be added to the regimen to attenuate formation of efficacy-reducing antidrug antibodies.

Final Thoughts

When managing children with psoriasis, it is important for dermatologists to appropriately educate guardians and children on the disease course, as well as consider the psychological, emotional, social, and financial factors that may direct decision-making regarding optimal therapeutics. Dermatologists should consider collaboration with the child’s primary care physician and other specialists to ensure that all needs are met.

These guidelines provide a framework agreed upon by numerous experts in pediatric psoriasis, but they are limited by gaps in the research. There still is much to be learned regarding the pathophysiology of psoriasis; the risk for developing comorbidities during adulthood; and the efficacy and safety of certain therapeutics, particularly biologics, in pediatric patients with psoriasis.

In November 2019, the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) released their first set of recommendations for the management of pediatric psoriasis.¹ The pediatric guidelines discuss methods of quantifying disease severity in children, triggers and comorbidities, and the efficacy and safety of various therapeutic agents. This review aims to discuss, in a condensed form, special considerations unique to the management of children with psoriasis as presented in the guidelines as well as grade A– and grade B–level treatment recommendations (Table).

Quantifying Psoriasis Severity in Children

Percentage body surface area (BSA) involvement is the most common mode of grading psoriasis severity, with less than 3% BSA involvement being considered mild, 3% to 10% BSA moderate, and more than 10% severe disease. In children, the standard method of measuring BSA is the rule of 9’s: the head and each arm make up 9% of the total BSA, each leg and the front and back of the torso respectively each make up 18%, and the genitalia make up 1%. It also is important to consider impact on quality of life, which may be remarkable in spite of limited BSA involvement. The children’s dermatology life quality index score may be utilized in combination with affected BSA to determine the burden of psoriasis in context of impact on daily life. This metric is available in both written and cartoon form, and it consists of 10 questions that include variables such as severity of itch, impact on social life, and effects on sleep. Most notably, this tool incorporates pruritus,² which generally is addressed inadequately in pediatric psoriasis.

Triggers and Comorbidities in Pediatric Patients

In children, it is important to identify and eliminate modifiable factors that may prompt psoriasis flares. Infections, particularly group A beta-hemolytic streptococcal infections, are a major trigger in neonates and infants. Other exacerbating factors in children include emotional stress, secondhand cigarette smoke, Kawasaki disease, and withdrawal from systemic corticosteroids.

Psoriatic arthritis (PsA) is a burdensome comorbidity affecting children with psoriasis. The prevalence of joint disease is 15-times greater in children with psoriasis vs those without,³ and 80% of children with PsA develop rheumatologic symptoms, which typically include oligoarticular disease and dactylitis in infants and girls and enthesitis and axial joint involvement in boys and older children, years prior to the onset of cutaneous disease.⁴ Uveitis often occurs in children with psoriasis and PsA but not in those with isolated cutaneous disease.

Compared to unaffected children, pediatric patients with psoriasis have greater prevalence of metabolic and cardiovascular risk factors during childhood, including central obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, atherosclerosis, arrythmia, and valvular heart disease. Family history of obesity increases the risk for early-onset development of cutaneous lesions,^5,6 and weight reduction may alleviate severity of psoriasis lesions.⁷ In the United States, many of the metabolic associations observed are particularly robust in Black and Hispanic children vs those of other races. Furthermore, the prevalence of inflammatory bowel disease is 3- to 4-times higher in children with psoriasis compared to those without.

As with other cutaneous diseases, it is important to be aware of social and mental health concerns in children with psoriasis. The majority of pediatric patients with psoriasis experience name-calling, shaming, or bullying, and many have concerns from skin shedding and malodor. Independent risk for depression after the onset of psoriasis is high. Affected older children and adolescents are at increased risk for alcohol and drug abuse as well as eating disorders.

Despite these identified comorbidities, there are no unique screening recommendations for arthritis, ophthalmologic disease, metabolic disease, cardiovascular disease, gastrointestinal tract disease, or mental health issues in children with psoriasis. Rather, these patients should be monitored according to the American Academy of Pediatrics or American Diabetes Association guidelines for all pediatric patients.^8,9 Nonetheless, educating patients and guardians about these potential issues may be warranted.

Topical Therapies

For children with mild to moderate psoriasis, topical therapies are first line. Despite being off label, topical corticosteroids are the mainstay of therapy for localized psoriatic plaques in children. Topical vitamin D analogues—calcitriol and calcipotriol/calcipotriene—are highly effective and well tolerated, and they frequently are used in combination with topical corticosteroids. Topical calcineurin inhibitors, namely tacrolimus, also are used off label but are considered first line for sensitive regions of the skin in children, including the face, genitalia, and body folds. There currently is limited evidence for supporting the use of the topical vitamin A analogue tazarotene in children with psoriasis, though some consider its off-label use effective for pediatric nail psoriasis. It also may be used as an adjunct to topical corticosteroids to minimize irritation.

Although there is no gold standard topical regimen, combination therapy with a high-potency topical steroid and topical vitamin D analogue commonly is used to minimize steroid-induced side effects. For the first 2 weeks of treatment, they each may be applied once daily or mixed together and applied twice daily. For subsequent maintenance, topical calcipotriene may be applied on weekdays and topical steroids only on weekends. Combination calcipotriol–betamethasone dipropionate also is available as cream, ointment, foam, and suspension vehicles for use on the body and scalp in children aged 12 years and older. Tacrolimus ointment 0.1% may be applied in a thin layer up to twice daily. Concurrent emollient use also is recommended with these therapies.

Health care providers should educate patients and guardians about the potential side effects of topical therapies. They also should provide explicit instructions for amount, site, frequency, and duration of application. Topical corticosteroids commonly result in burning on application and may potentially cause skin thinning and striae with overuse. Topical vitamin D analogues may result in local irritation that may be improved by concurrent emollient use, and they generally should be avoided on sensitive sites. Topical calcineurin inhibitors are associated with burning, stinging, and pruritus, and the US Food and Drug Administration has issued a black-box warning related to risk for lymphoma with their chronic intermittent use. However, it was based on rare reports of lymphoma in transplant patients taking oral calcineurin inhibitors; no clinical trials to date in humans have demonstrated an increased risk for malignancy with topical calcineurin inhibitors.¹⁰ Tazarotene should be used cautiously in females of childbearing age given its teratogenic potential.

Children younger than 7 years are especially prone to suppression of the hypothalamic-pituitary-adrenal axis from topical corticosteroid therapy and theoretically hypercalcemia and hypervitaminosis D from topical vitamin D analogues, as their high BSA-to-volume ratio increases potential for systemic absorption. Children should avoid occlusive application of topical vitamin D analogues to large areas of the skin. Monitoring of vitamin D metabolites in the serum may be considered if calcipotriene or calcipotriol application to a large BSA is warranted.

Light-Based Therapy

In children with widespread psoriasis or those refractory to topical therapy, phototherapy may be considered. Narrowband UVB (311- to 313-nm wavelength) therapy is considered a first-line form of phototherapy in pediatric psoriasis. Mineral oil or emollient pretreatment to affected areas may augment the efficacy of UV-based treatments.¹¹ Excimer laser and UVA also may be efficacious, though evidence is limited in children. Treatment is recommended to start at 3 days a week, and once improvement is seen, the frequency can be decreased to 2 days a week. Once desired clearance is achieved, maintenance therapy can be continued at even longer intervals. Adjunctive use of tar preparations may potentiate the efficacy of phototherapy, though there is a theoretical increased risk for carcinogenicity with prolonged use of coal tar. Side effects of phototherapy include erythema, blistering hyperpigmentation, and pruritus. Psoralen is contraindicated in children younger than 12 years. All forms of phototherapy are contraindicated in children with generalized erythroderma and cutaneous cancer syndromes. Other important pediatric-specific considerations include anxiety that may be provoked by UV light machines and inconvenience of frequent appointments.

Nonbiologic Systemic Therapies

Systemic therapies may be considered in children with recalcitrant, widespread, or rapidly progressing psoriasis, particularly if the disease is accompanied by severe emotional and psychological burden. These drugs, which include methotrexate, cyclosporine, and acitretin (see eTable for recommended dosing), are advantageous in that they may be combined with other therapies; however, they have potential for dangerous toxicities.

Methotrexate is the most frequently utilized systemic therapy for psoriasis worldwide in children because of its low cost, once-weekly dosing, and the substantial amount of long-term efficacy and safety data available in the pediatric population. It is slow acting initially but has excellent long-term efficacy for nearly every subtype of psoriasis. The most common side effect of methotrexate is gastrointestinal tract intolerance. Nonetheless, adverse events are rare in children without prior history, with 1 large study (N=289) reporting no adverse events in more than 90% of patients aged 9 to 14 years treated with methotrexate.¹² Current guidelines recommend monitoring for bone marrow suppression and elevated transaminase levels 4 to 6 days after initiating treatment.¹ The absolute contraindications for methotrexate are pregnancy and liver disease, and caution should be taken in children with metabolic risk factors. Adolescents must be counseled regarding the elevated risk for hepatotoxicity associated with alcohol ingestion. Methotrexate therapy also requires 1 mg folic acid supplementation 6 to 7 days a week, which decreases the risk for developing folic acid deficiency and may decrease gastrointestinal tract intolerance and hepatic side effects that may result from therapy.

Cyclosporine is an effective and well-tolerated option for rapid control of severe psoriasis in children. It is useful for various types of psoriasis but generally is reserved for more severe subtypes, such as generalized pustular psoriasis, erythrodermic psoriasis, and uncontrolled plaque psoriasis. Long-term use of cyclosporine may result in renal toxicity and hypertension, and this therapy is absolutely contraindicated in children with kidney disease or hypertension at baseline. It is strongly recommended to evaluate blood pressure every week for the first month of therapy and at every subsequent follow-up visit, which may occur at variable intervals based on the judgement of the provider. Evaluation before and during treatment with cyclosporine also should include a complete blood cell count, complete metabolic panel, and lipid panel.

Systemic retinoids have a unique advantage over methotrexate and cyclosporine in that they are not immunosuppressive and therefore are not contraindicated in children who are very young or immunosuppressed. Children receiving systemic retinoids also can receive routine live vaccines—measles-mumps-rubella, varicella zoster, and rotavirus—that are contraindicated with other systemic therapies. Acitretin is particularly effective in pediatric patients with diffuse guttate psoriasis, pustular psoriasis, and palmoplantar psoriasis. Narrowband UVB therapy has been shown to augment the effectiveness of acitretin in children, which may allow for reduced acitretin dosing. Pustular psoriasis may respond as quickly as 3 weeks after initiation, whereas it may take 2 to 3 months before improvement is noticed in plaque psoriasis. Side effects of retinoids include skin dryness, hyperlipidemia, and gastrointestinal tract upset. The most severe long-term concern is skeletal toxicity, including premature epiphyseal closure, hyperostosis, periosteal bone formation, and decreased bone mineral density.¹ Vitamin A derivatives also are known teratogens and should be avoided in females of childbearing potential. Lipids and transaminases should be monitored routinely, and screening for depression and psychiatric symptoms should be performed frequently.¹

When utilizing systemic therapies, the objective should be to control the disease, maintain stability, and ultimately taper to the lowest effective dose or transition to a topical therapy, if feasible. Although no particular systemic therapy is recommended as first line for children with psoriasis, it is important to consider comorbidities, contraindications, monitoring frequency, mode of administration (injectable therapies elicit more psychological trauma in children than oral therapies), and expense when determining the best choice.

Biologics

Biologic agents are associated with very high to total psoriatic plaque clearance rates and require infrequent dosing and monitoring. However, their use may be limited by cost and injection phobias in children as well as limited evidence for their efficacy and safety in pediatric psoriasis. Several studies have established the safety and effectiveness of biologics in children with plaque psoriasis (see eTable for recommended dosing), whereas the evidence supporting their use in treating pustular and erythrodermic variants are limited to case reports and case series. The tumor necrosis factor α (TNF-α) inhibitor etanercept has been approved for use in children aged 4 years and older, and the IL-12/IL-23 inhibitor ustekinumab is approved in children aged 6 years and older. Other TNF-α inhibitors, namely infliximab and adalimumab, commonly are utilized off label for pediatric psoriasis. The most common side effect of biologic therapies in pediatric patients is injection-site reactions.¹ Prior to initiating therapy, children must undergo tuberculosis screening either by purified protein derivative testing or IFN-γ release assay. Testing should be repeated annually in individuals taking TNF-α inhibitors, though the utility of repeat testing when taking biologics in other classes is not clear. High-risk patients also should be screened for human immunodeficiency virus and hepatitis. Follow-up frequency may range from every 3 months to annually, based on judgement of the provider. In children who develop loss of response to biologics, methotrexate can be added to the regimen to attenuate formation of efficacy-reducing antidrug antibodies.

Final Thoughts

When managing children with psoriasis, it is important for dermatologists to appropriately educate guardians and children on the disease course, as well as consider the psychological, emotional, social, and financial factors that may direct decision-making regarding optimal therapeutics. Dermatologists should consider collaboration with the child’s primary care physician and other specialists to ensure that all needs are met.

These guidelines provide a framework agreed upon by numerous experts in pediatric psoriasis, but they are limited by gaps in the research. There still is much to be learned regarding the pathophysiology of psoriasis; the risk for developing comorbidities during adulthood; and the efficacy and safety of certain therapeutics, particularly biologics, in pediatric patients with psoriasis.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Psoriasis and atopic dermatitis (AD) can impact quality of life (QOL) in pediatric patients, warranting early recognition and treatment.¹ Topical agents often are inadequate to treat moderate to severe disease, but the potential toxicity of systemic agents, which largely include immunosuppressives, limit their use in this population despite their effectiveness. Our expanding knowledge of the pathogenesis of psoriasis (tumor necrosis factor [TNF] α and IL-23/T_H17 pathways) and AD has led to targeted interventions, particularly monoclonal antibody biologics, which have revolutionized treatment for affected adults and more recently children. Several agents are approved by the US Food and Drug Administration (FDA) for pediatric psoriasis, and dupilumab is approved for pediatric AD. Herein, we discuss the latest developments in the treatment landscape for pediatric psoriasis and AD.

Pediatric Psoriasis

Methotrexate (MTX) and cyclosporine have been FDA approved for psoriasis in adults since 1972 and 1997, respectively.² Before biologics, MTX was the primary systemic agent used to treat pediatric psoriasis, given its lower toxicity vs cyclosporine. The TNF-α inhibitor etanercept became the first FDA-approved biologic for pediatric psoriasis in 2016. Adalimumab has been available in Europe for children since 2015 but is not FDA approved. Certolizumab, a pegylated TNF-α inhibitor that distinctly fails to cross the placental barrier currently is in clinical trials (ClinicalTrials.gov identifier NCT04123795). Tumor necrosis factor α inhibitors have shown more rapid onset and greater efficacy during the first 16 weeks of use than MTX, including a head-to-head trial comparing MTX to adalimumab.³ A recent real-world study showed that pediatric patients receiving biologics, primarily TNF-α inhibitors, were more likely to achieve psoriasis area and severity index (PASI) 75 or clear/almost clear status (similar to PASI 90) than MTX and had higher drug survival rates.⁴

Ustekinumab targets both IL-12 and IL-23, which share the IL-23 receptor p40 subunit. It was the first biologic to target IL-23, which promotes the proliferation and survival of helper T cells (T_H17). Ustekinumab has led to greater reductions in PASI scores than TNF-α inhibitors.^5,6 Pediatric trials of guselkumab, risankizumab, and tildrakizumab, all targeting the IL-23 receptor–specific p19 subunit, are completed or currently recruiting (NCT03451851, NCT03997786, NCT04435600). Ixekizumab is the first IL-17A–targeting biologic approved for children.⁷ Secukinumab and the IL-17 receptor inhibitor brodalumab are in pediatric trials (NCT03668613, NCT04305327, NCT03240809). One potential issue with T_H17 pathway inhibitors is their association with inflammatory bowel disease, a contraindication when considering if a patient is a potential candidate for treatment.

Skin disease can profoundly affect QOL during childhood and adolescence, a critical time for psychosocial development. In psoriasis, improvement in QOL is proportional to clearance and is greater when PASI 90 is achieved vs PASI 75.⁸ The high efficacy of IL-23 and IL-17A pathway inhibitors now makes achieving at least PASI 90 the new standard, which can be reached in most patients.

Pediatric AD

For AD in the pediatric population, systemic treatments primarily include corticosteroids, mycophenolate mofetil, azathioprine, cyclosporine, and MTX. Although cyclosporine was the favored systemic agent among pediatric dermatologists in one study,⁹ claims data analyses show that systemic corticosteroids are used much more often overall, prescribed in 24.4% (116,635 total cases) of children with AD vs nonsteroidal immunosuppressants in less than 0.5%.¹⁰ Systemic steroids are impractical given their side effects and risk for disease rebound; however, no immunosuppressants are safe for long-term use, and all require frequent laboratory monitoring. The development of biologics for AD largely involves targeting T_H2-driven inflammation.¹¹ Dupilumab is the only FDA-approved biologic for moderate to severe pediatric AD, including in patients as young as 6 years of age. Dupilumab inhibits activation of the IL-4Rα subunit, thereby blocking responses to its ligands, IL-4 and IL-13. Phase 3 trials are now underway in children aged 6 months to 5 years (NCT02612454, NCT03346434). The concomitant ameliorative effects of dupilumab on asthma and other allergic disorders, occurring in approximately 90% of children with moderate to severe AD, is an added benefit.¹² Although dupilumab does not appear to modify the disease course in children with AD, the possibility that early introduction could reduce the risk for later developing allergic disease is intriguing.

Adolescent trials have been started for lebrikizumab (NCT04392154) and have been completed for tralokinumab (NCT03160885). Both agents selectively target IL-13 to block T_H2 pathway inflammation. The only reported adverse effects of IL-4Rα and IL-13 inhibitors have been injection-site pain/reactions and increased conjunctivitis.¹³

The only other biologic for AD currently in clinical trials for adolescents is nemolizumab, targeting the receptor for IL-31, a predominantly T_H2 cytokine that causes pruritus (NCT03989349). In adults, nemolizumab has shown rapid and potent suppression of itch (but not inflammation) without adding topical corticosteroids.¹⁴

Advantages of Biologics and Laboratory Monitoring

By targeting specific cytokines, biologics have greater and more rapid efficacy, fewer side effects, fewer drug interactions, less frequent dosing, and less immunosuppression compared to other systemic agents.^3,4,15,16

Recent pediatric-specific guidelines for psoriasis recommend baseline monitoring for tuberculosis for all biologics but yearly tuberculosis testing only for TNF-α inhibitors unless the individual patient is at increased risk.² No tuberculosis testing is needed for dupilumab, and no other laboratory monitoring is recommended for any biologic in children unless warranted by risk. This difference in recommended monitoring suggests the safety of biologics and is advantageous in managing pediatric therapy.

Unanswered Questions: Vaccines and Antidrug Antibodies

Although administration of killed vaccines is considered safe with all approved biologics, questions remain about the safety of administering live vaccines while on biologics, a particularly pertinent issue in younger children treated with dupilumab and other biologics for AD. Another unanswered question is the potential reduction in clinical response and drug durability with intermittent use of biologics due to the potential development of neutralizing antidrug antibodies (ADAs). The ability to discontinue medication intermittently is desirable, both to determine the natural course of the underlying disease and give a holiday as tolerated. Newer biologics are thought to have lower immunogenicity and less frequent ADA development.^17-19 Even with TNF-α inhibitors, the presence of anti-ADAs is not temporally related to response in children with psoriasis.²⁰ Long-term outcomes of the use of biologics in adults have been reassuring, and safety profiles of biologics studied thus far appear to be similar in children.^21,22 However, understanding the potential long-term effects from the use of newly approved and emerging biologics in the pediatric population will require decades of study to ensure safety, including nonrandomized studies and postmarketing reports from regulatory agencies.

Cost Considerations

Biologics are disease and QOL altering for children with moderate to severe psoriasis or AD; however, access to biologics often is an obstacle for patients and practitioners. Biologics cost $30,000 to $60,000 annually, while conventional systemic treatments such as MTX, cyclosporine, and acitretin cost $100 to $3000 annually, raising the question of cost effectiveness. In 2016, the Institute for Clinical and Economic Review concluded that biologics for psoriasis had reasonably good value based on improved QOL and concluded in 2017 that dupilumab had a benefit that outweighed its cost.^23,24 Prior authorizations and multiple appeals have been necessary to obtain approval, especially in the pediatric population.²⁵ This difficulty highlights the need for programs to cover the cost of biologics for all children, as well as registries to further assess effectiveness and long-term safety, especially compared to traditional systemic agents.

On the Horizon

Clinical trials for other therapies for children and adolescents are ongoing. Details on recommended dosing, approval status, and efficacy in trials are provided in the eTable. Given their high efficacy in adults with psoriasis, IL-23–specific and T_H17 pathway biologics likely are similarly efficacious and raise the bar for the expectation of achieving PASI 90 and PASI 100 responses. The long-term safety, durability of responses, and ability to modify disease, particularly when started early in life (eg, preadolescence) and early in the disease course, remains to be determined.

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

The investigational monoclonal antibody mirikizumab performed more robustly against placebo overall – and the interleukin-17 inhibitor secukinumab at key endpoints – for treatment of moderate to severe psoriasis, according to new long-term OASIS-2 trial data.

Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.

If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate to severe psoriasis, said OASIS-2 lead investigator Kim A. Papp, MD, PhD, founder and president of Probity Medical Research in Waterloo, Ont.

But Dr. Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the virtual annual European Academy of Dermatology and Venereology Congress.

“Probably the most important takeaway here is that we may have another option to choose from,” Dr. Papp said in an interview. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”

“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added. Psoriasis biologics “are increasingly competent, compared to medications we had even 5 or 10 years ago ... but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”

The multicenter trial included 1,465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.

The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.

Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16, compared with placebo.

Major secondary endpoints were PASI 75 and PASI 100, compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 noninferiority, compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority, compared with secukinumab at week 52.

More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).

At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients versus 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients versus 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients versus 42.9% of secukinumab patients.

Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Dr. Papp said. One death occurred in a mirikizumab patient from acute MI, which was deemed unrelated to the study drug.

Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki (Greece), said the results indicate that dermatologists “should not be afraid to use” mirikizumab long term if it is approved by the Food and Drug Administration.

“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Dr. Trakatelli said in an interview. “A new biologic is always welcome because we do see patients not responding to other treatment.”

But Dr. Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”

“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Dr. Trakatelli, chair of the EADV education committee.

Dr. Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”

“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Dr. Papp added.

But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Dr. Papp stressed.

“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”

The trial was funded by Lilly. Dr. Papp disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Dr. Trakatelli is a speaker for Novartis.

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

The investigational monoclonal antibody mirikizumab performed more robustly against placebo overall – and the interleukin-17 inhibitor secukinumab at key endpoints – for treatment of moderate to severe psoriasis, according to new long-term OASIS-2 trial data.

Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.

If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate to severe psoriasis, said OASIS-2 lead investigator Kim A. Papp, MD, PhD, founder and president of Probity Medical Research in Waterloo, Ont.

But Dr. Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the virtual annual European Academy of Dermatology and Venereology Congress.

“Probably the most important takeaway here is that we may have another option to choose from,” Dr. Papp said in an interview. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”

“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added. Psoriasis biologics “are increasingly competent, compared to medications we had even 5 or 10 years ago ... but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”

The multicenter trial included 1,465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.

The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.

Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16, compared with placebo.

Major secondary endpoints were PASI 75 and PASI 100, compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 noninferiority, compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority, compared with secukinumab at week 52.

More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).

At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients versus 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients versus 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients versus 42.9% of secukinumab patients.

Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Dr. Papp said. One death occurred in a mirikizumab patient from acute MI, which was deemed unrelated to the study drug.

Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki (Greece), said the results indicate that dermatologists “should not be afraid to use” mirikizumab long term if it is approved by the Food and Drug Administration.

“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Dr. Trakatelli said in an interview. “A new biologic is always welcome because we do see patients not responding to other treatment.”

But Dr. Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”

“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Dr. Trakatelli, chair of the EADV education committee.

Dr. Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”

“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Dr. Papp added.

But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Dr. Papp stressed.

“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”

The trial was funded by Lilly. Dr. Papp disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Dr. Trakatelli is a speaker for Novartis.

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

The investigational monoclonal antibody mirikizumab performed more robustly against placebo overall – and the interleukin-17 inhibitor secukinumab at key endpoints – for treatment of moderate to severe psoriasis, according to new long-term OASIS-2 trial data.

Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.

If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate to severe psoriasis, said OASIS-2 lead investigator Kim A. Papp, MD, PhD, founder and president of Probity Medical Research in Waterloo, Ont.

But Dr. Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the virtual annual European Academy of Dermatology and Venereology Congress.

“Probably the most important takeaway here is that we may have another option to choose from,” Dr. Papp said in an interview. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”

“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added. Psoriasis biologics “are increasingly competent, compared to medications we had even 5 or 10 years ago ... but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”

The multicenter trial included 1,465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.

The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.

Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16, compared with placebo.

Major secondary endpoints were PASI 75 and PASI 100, compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 noninferiority, compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority, compared with secukinumab at week 52.

More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).

At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients versus 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients versus 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients versus 42.9% of secukinumab patients.

Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Dr. Papp said. One death occurred in a mirikizumab patient from acute MI, which was deemed unrelated to the study drug.

Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki (Greece), said the results indicate that dermatologists “should not be afraid to use” mirikizumab long term if it is approved by the Food and Drug Administration.

“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Dr. Trakatelli said in an interview. “A new biologic is always welcome because we do see patients not responding to other treatment.”

But Dr. Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”

“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Dr. Trakatelli, chair of the EADV education committee.

Dr. Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”

“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Dr. Papp added.

But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Dr. Papp stressed.

“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”

The trial was funded by Lilly. Dr. Papp disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Dr. Trakatelli is a speaker for Novartis.

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

Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, a new international phase 2b research suggests.

An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.

“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.

“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”

Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.

Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.

“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”

The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”

Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.

The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.

At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).

This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).

“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”

Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.

Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.

It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.

“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”

The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.

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

Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, a new international phase 2b research suggests.

An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.

“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.

“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”

Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.

Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.

“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”

The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”

Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.

The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.

At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).

This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).

“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”

Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.

Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.

It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.

“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”

The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.

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

Delgocitinib cream shows a dose-dependent response in easing chronic hand eczema, a common and difficult-to-treat disorder for which few other topical options are available, a new international phase 2b research suggests.

An investigational pan–Janus kinase inhibitor that blocks all four members of the JAK family, twice-daily delgocitinib doses of 8 mg/g and 20 mg/g demonstrated the highest efficacy in adults with mild to severe chronic hand eczema. By week 16, nearly 40% of patients receiving either dose were clear or almost clear of symptoms.

“By mode of action, we think delgocitinib is more selective in the way of acting,” said lead investigator Margitta Worm, MD, PhD, of the department of dermatology, venereology, and allergology at Charité University Hospital in Berlin, during a presentation of the results at the virtual annual congress of the European Academy of Dermatology and Venereology.

“We do know that JAKs play an important role in chronic inflammation and interfering with the JAK pathway can have anti-inflammatory effects,” Dr. Worm said in an interview. “Whenever it’s possible to use a molecule topically or locally, it’s advantageous for patients because it’s only acting where you apply it and there are no systemic side effects.”

Defined as lasting more than 3 months or relapsing twice or more within a year, chronic hand eczema is a particularly problematic form of atopic dermatitis because “we need our hands every day for almost every activity, so having eczema on your hands has a huge impact on quality of life,” Dr. Worm said.

Many people whose hands are integral to their occupations also have trouble working because of the disorder, she explained. But current topical treatments are limited to emollients, corticosteroids, and calcineurin inhibitors.

“Topical corticosteroids are efficacious, but can cause skin atrophy,” she said. “Their long-term side-effect profile limits their use.”

The number of patients in each treatment group was too small to focus on different subtypes of chronic hand eczema, “but this is something that will probably be looked at in the future,” Dr. Worm said. “At the moment it’s nice to see a dose-dependent clinical efficacy and good tolerability, and now we have to wait for phase 3 data in the future.”

Dr. Worm and colleagues aimed to establish the dose-response relationship of twice-daily applications of delgocitinib cream in doses of 1, 3, 8, and 20 mg/g and a delgocitinib cream vehicle for 16 weeks. The 258 participants (61% women; average age, 46 years) were randomly assigned in equal groups to each dose of delgocitinib cream or the vehicle cream twice daily at centers in Denmark, Germany, and the United States.

The primary endpoint for the double-blind, 26-center trial was the proportion of patients who achieved an Investigator’s Global Assessment score of 0 (“clear”) or 1 (“almost clear”), with a 2-point or higher improvement from baseline over the study period. A key secondary endpoint was a change in the Hand Eczema Severity Index (HECSI) from baseline to week 16.

At week 16, a statistically significant dose response was established for both primary and secondary endpoints (P < .025). More patients in the delgocitinib 8-mg/g and 20-mg/g groups met the primary endpoint (36.5% and 37.7%, respectively) than patients in the 1-mg/g and 3-mg/g groups (21.2% and 7.8%, respectively) and vehicle group (8%, P = .0004).

This primary skin clearance effect at week 16 was demonstrated from week 4 in the 8-mg/g group and week 6 in the 20-mg/g group. But all active doses achieved a statistically significant greater jump in HECSI from baseline to week 16 than the vehicle cream (P < .05).

“The strength of the trial is that there were different concentrations of the substance used,” Dr. Worm said. “When you look to the results, you can demonstrate a dose-dependent clinical efficacy. This is of great value to really compare the efficacy of single doses.”

Most adverse events reported were not considered treatment related and were mild or moderate. The most frequently reported side effects were nasopharyngitis, eczema, and headache.

Commenting on the results, Asli Bilgic, MD, from Akdeniz University in Antalya, Turkey, who was not involved with the study, said that phase 3 studies of delgocitinib should probe further into the effects of the 8-mg/g dosage in this patient group since it appears to show similar efficacy and safety to 20 mg/g.

It’s important for research to focus on hand eczema “because it’s a very common disease, and treatment options are really sparse,” Dr. Bilgic said in an interview.

“Especially in the COVID era, many health care professionals, along with cleaning, catering, and mechanical jobs” are essential workers affected by the condition, she said. “It affects people’s self-esteem and their ability to do their job.”

The study was funded by LEO Pharma. Dr. Worm received lecture honoraria from LEO Pharma. Dr. Bilgic disclosed no relevant financial relationships.

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

The available data suggest that the risks posed by COVID-19 infection to patients with psoriasis, including those on therapies that affect immune function, are modest at most, according to a summary of published studies and expert opinions summarized at the annual Coastal Dermatology Symposium, held virtually.

For patients with psoriasis concerned about their outcome if infected with COVID-19, “there is no evidence to support stopping biologics or systemic agents, so I am asking my patients to continue,” Kristina C. Duffin, MD, professor and chair of dermatology at the University of Utah, Salt Lake City, said at the meeting.

The National Psoriasis Foundation, which created a COVID-19 task force and maintains a COVID-19 Resource Center on its website, has provided similar advice. Many statements are phrased cautiously and clinicians are encouraged to practice shared decision-making, but the NPF guidance supports continuing effective therapy – or, in newly diagnosed patients, starting effective therapy – among those who are not infected with SARS-CoV2.

Patients with a new diagnosis of psoriasis “should be aware that untreated psoriatic disease is associated with serious impact on physical and emotional health, and in the case of psoriatic arthritis, can lead to permanent joint damage and disability,” according to the NPF guidance.

Overall, the “existing data generally suggest” that most treatments for psoriasis and psoriatic arthritis “do not meaningfully alter the risks of contracting SARS-CoV2 or having a worse course of COVID-19 illness,” the current guidance states. Yet, because of limited data this “is not known with certainty.”

Chronic systemic steroids are an exception. In a review of recently published studies evaluating whether psoriasis or its therapies increase risk of adverse outcomes in patients with COVID-19 infection, Dr. Duffin pointed to several that associated systemic steroids with hospitalization or other markers of severe disease.

The NPF guidance also recommends avoiding chronic systemic steroids in patients with psoriasis during the current COVID-19 era “if possible.” In patients with psoriatic arthritis who require systemic steroids, the guidance recommends “the lowest dose necessary to achieve the desired therapeutic effect.”

This is not necessarily true in patients with psoriasis and COVID-19 infection. Based on the potential for systemic steroids to improve outcomes in hospitalized COVID-19 patients requiring oxygen, steroids “should not be withheld” even when the justification is concern about the potential risk of flares with withdrawal, according to the NPF guidance statement.

The NPF guidance specifically cautions against use of hydroxychloroquine or chloroquine for prevention or treatment of COVID-19. In addition to an uncertain benefit, these antimalarial drugs have been associated previously with flares of psoriasis.

Dr. Duffin agreed and went on to warn that COVID-19 infection itself is a potential trigger for flares. She cited two published case reports of flares associated with psoriasis. Although one patient had also been exposed to hydroxychloroquine, she said the risk of psoriasis-induced flare “makes sense” based on previous associations made between flares and other viral infections and stress.

In patients with psoriasis who contract COVID-19 infection, Dr. Duffin concurred with the NPF guidance that management decisions should be made on a “case-by-case basis.” Although the NPF guidance states that “most patients can restart psoriasis and/or psoriatic arthritis treatments after complete resolution of COVID-19 symptoms,” no specific advice was offered on the decision to stop treatments.

For protecting psoriasis patients from infection and managing COVID-19 in those who become infected, much of the NPF advice is consistent with that offered to patients without psoriasis. This involves practicing infection control that reduces risk of transmission. Both the NPF guidance and Dr. Duffin suggested telemedicine is appropriate for limiting in-patient visits under pandemic conditions.

Although patients with psoriasis are more likely than the general population to have the comorbidities associated with bad COVID-19 infection outcomes, according to the NPF guidance, Dr. Duffin called the overall data evaluating susceptibility among psoriasis patients “reassuring.” She cautioned that the data are still limited, but the evidence so far suggests that neither psoriasis nor biologics are independent risk factors for acquiring COVID-19 or having a worse outcome if infected.

Yet, more definitive data are needed, and Dr. Duffin advised clinicians and patients to consult the NPF website for updates. “More up-to-date information will certainly be added as we go forward,” she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

This NPF task force on COVID-19 is meeting every 2 weeks, according to Joel M. Gelfand, MD, professor of dermatology, University of Pennsylvania, Philadelphia, and cochair of the task force. Dr. Gelfand reported that updates are based on a discussion of the available data.

“We will be releasing additional recommendations as necessary based on the developments,” he said in an interview. Updates are not necessarily required at this frequency but can be if appropriate. The goal is to keep recommendations current and evidence-based.

Dr. Duffin reported financial relationships with Amgen, AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Siena, and UCB. Dr. Gelfand reported financial relationships with AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, Roche, and UCB.

This publication and Global Academy for Medical Education are owned by the same parent company.
 

The available data suggest that the risks posed by COVID-19 infection to patients with psoriasis, including those on therapies that affect immune function, are modest at most, according to a summary of published studies and expert opinions summarized at the annual Coastal Dermatology Symposium, held virtually.

For patients with psoriasis concerned about their outcome if infected with COVID-19, “there is no evidence to support stopping biologics or systemic agents, so I am asking my patients to continue,” Kristina C. Duffin, MD, professor and chair of dermatology at the University of Utah, Salt Lake City, said at the meeting.

The National Psoriasis Foundation, which created a COVID-19 task force and maintains a COVID-19 Resource Center on its website, has provided similar advice. Many statements are phrased cautiously and clinicians are encouraged to practice shared decision-making, but the NPF guidance supports continuing effective therapy – or, in newly diagnosed patients, starting effective therapy – among those who are not infected with SARS-CoV2.

Patients with a new diagnosis of psoriasis “should be aware that untreated psoriatic disease is associated with serious impact on physical and emotional health, and in the case of psoriatic arthritis, can lead to permanent joint damage and disability,” according to the NPF guidance.

Overall, the “existing data generally suggest” that most treatments for psoriasis and psoriatic arthritis “do not meaningfully alter the risks of contracting SARS-CoV2 or having a worse course of COVID-19 illness,” the current guidance states. Yet, because of limited data this “is not known with certainty.”

Chronic systemic steroids are an exception. In a review of recently published studies evaluating whether psoriasis or its therapies increase risk of adverse outcomes in patients with COVID-19 infection, Dr. Duffin pointed to several that associated systemic steroids with hospitalization or other markers of severe disease.

The NPF guidance also recommends avoiding chronic systemic steroids in patients with psoriasis during the current COVID-19 era “if possible.” In patients with psoriatic arthritis who require systemic steroids, the guidance recommends “the lowest dose necessary to achieve the desired therapeutic effect.”

This is not necessarily true in patients with psoriasis and COVID-19 infection. Based on the potential for systemic steroids to improve outcomes in hospitalized COVID-19 patients requiring oxygen, steroids “should not be withheld” even when the justification is concern about the potential risk of flares with withdrawal, according to the NPF guidance statement.

The NPF guidance specifically cautions against use of hydroxychloroquine or chloroquine for prevention or treatment of COVID-19. In addition to an uncertain benefit, these antimalarial drugs have been associated previously with flares of psoriasis.

Dr. Duffin agreed and went on to warn that COVID-19 infection itself is a potential trigger for flares. She cited two published case reports of flares associated with psoriasis. Although one patient had also been exposed to hydroxychloroquine, she said the risk of psoriasis-induced flare “makes sense” based on previous associations made between flares and other viral infections and stress.

In patients with psoriasis who contract COVID-19 infection, Dr. Duffin concurred with the NPF guidance that management decisions should be made on a “case-by-case basis.” Although the NPF guidance states that “most patients can restart psoriasis and/or psoriatic arthritis treatments after complete resolution of COVID-19 symptoms,” no specific advice was offered on the decision to stop treatments.

For protecting psoriasis patients from infection and managing COVID-19 in those who become infected, much of the NPF advice is consistent with that offered to patients without psoriasis. This involves practicing infection control that reduces risk of transmission. Both the NPF guidance and Dr. Duffin suggested telemedicine is appropriate for limiting in-patient visits under pandemic conditions.

Although patients with psoriasis are more likely than the general population to have the comorbidities associated with bad COVID-19 infection outcomes, according to the NPF guidance, Dr. Duffin called the overall data evaluating susceptibility among psoriasis patients “reassuring.” She cautioned that the data are still limited, but the evidence so far suggests that neither psoriasis nor biologics are independent risk factors for acquiring COVID-19 or having a worse outcome if infected.

Yet, more definitive data are needed, and Dr. Duffin advised clinicians and patients to consult the NPF website for updates. “More up-to-date information will certainly be added as we go forward,” she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

This NPF task force on COVID-19 is meeting every 2 weeks, according to Joel M. Gelfand, MD, professor of dermatology, University of Pennsylvania, Philadelphia, and cochair of the task force. Dr. Gelfand reported that updates are based on a discussion of the available data.

“We will be releasing additional recommendations as necessary based on the developments,” he said in an interview. Updates are not necessarily required at this frequency but can be if appropriate. The goal is to keep recommendations current and evidence-based.

Dr. Duffin reported financial relationships with Amgen, AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Siena, and UCB. Dr. Gelfand reported financial relationships with AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, Roche, and UCB.

This publication and Global Academy for Medical Education are owned by the same parent company.
 

The available data suggest that the risks posed by COVID-19 infection to patients with psoriasis, including those on therapies that affect immune function, are modest at most, according to a summary of published studies and expert opinions summarized at the annual Coastal Dermatology Symposium, held virtually.

For patients with psoriasis concerned about their outcome if infected with COVID-19, “there is no evidence to support stopping biologics or systemic agents, so I am asking my patients to continue,” Kristina C. Duffin, MD, professor and chair of dermatology at the University of Utah, Salt Lake City, said at the meeting.

The National Psoriasis Foundation, which created a COVID-19 task force and maintains a COVID-19 Resource Center on its website, has provided similar advice. Many statements are phrased cautiously and clinicians are encouraged to practice shared decision-making, but the NPF guidance supports continuing effective therapy – or, in newly diagnosed patients, starting effective therapy – among those who are not infected with SARS-CoV2.

Patients with a new diagnosis of psoriasis “should be aware that untreated psoriatic disease is associated with serious impact on physical and emotional health, and in the case of psoriatic arthritis, can lead to permanent joint damage and disability,” according to the NPF guidance.

Overall, the “existing data generally suggest” that most treatments for psoriasis and psoriatic arthritis “do not meaningfully alter the risks of contracting SARS-CoV2 or having a worse course of COVID-19 illness,” the current guidance states. Yet, because of limited data this “is not known with certainty.”

Chronic systemic steroids are an exception. In a review of recently published studies evaluating whether psoriasis or its therapies increase risk of adverse outcomes in patients with COVID-19 infection, Dr. Duffin pointed to several that associated systemic steroids with hospitalization or other markers of severe disease.

The NPF guidance also recommends avoiding chronic systemic steroids in patients with psoriasis during the current COVID-19 era “if possible.” In patients with psoriatic arthritis who require systemic steroids, the guidance recommends “the lowest dose necessary to achieve the desired therapeutic effect.”

This is not necessarily true in patients with psoriasis and COVID-19 infection. Based on the potential for systemic steroids to improve outcomes in hospitalized COVID-19 patients requiring oxygen, steroids “should not be withheld” even when the justification is concern about the potential risk of flares with withdrawal, according to the NPF guidance statement.

The NPF guidance specifically cautions against use of hydroxychloroquine or chloroquine for prevention or treatment of COVID-19. In addition to an uncertain benefit, these antimalarial drugs have been associated previously with flares of psoriasis.

Dr. Duffin agreed and went on to warn that COVID-19 infection itself is a potential trigger for flares. She cited two published case reports of flares associated with psoriasis. Although one patient had also been exposed to hydroxychloroquine, she said the risk of psoriasis-induced flare “makes sense” based on previous associations made between flares and other viral infections and stress.

In patients with psoriasis who contract COVID-19 infection, Dr. Duffin concurred with the NPF guidance that management decisions should be made on a “case-by-case basis.” Although the NPF guidance states that “most patients can restart psoriasis and/or psoriatic arthritis treatments after complete resolution of COVID-19 symptoms,” no specific advice was offered on the decision to stop treatments.

For protecting psoriasis patients from infection and managing COVID-19 in those who become infected, much of the NPF advice is consistent with that offered to patients without psoriasis. This involves practicing infection control that reduces risk of transmission. Both the NPF guidance and Dr. Duffin suggested telemedicine is appropriate for limiting in-patient visits under pandemic conditions.

Although patients with psoriasis are more likely than the general population to have the comorbidities associated with bad COVID-19 infection outcomes, according to the NPF guidance, Dr. Duffin called the overall data evaluating susceptibility among psoriasis patients “reassuring.” She cautioned that the data are still limited, but the evidence so far suggests that neither psoriasis nor biologics are independent risk factors for acquiring COVID-19 or having a worse outcome if infected.

Yet, more definitive data are needed, and Dr. Duffin advised clinicians and patients to consult the NPF website for updates. “More up-to-date information will certainly be added as we go forward,” she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

This NPF task force on COVID-19 is meeting every 2 weeks, according to Joel M. Gelfand, MD, professor of dermatology, University of Pennsylvania, Philadelphia, and cochair of the task force. Dr. Gelfand reported that updates are based on a discussion of the available data.

“We will be releasing additional recommendations as necessary based on the developments,” he said in an interview. Updates are not necessarily required at this frequency but can be if appropriate. The goal is to keep recommendations current and evidence-based.

Dr. Duffin reported financial relationships with Amgen, AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Siena, and UCB. Dr. Gelfand reported financial relationships with AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, Roche, and UCB.

This publication and Global Academy for Medical Education are owned by the same parent company.
 

Non-White patient participation in phase 3 therapeutic trials for plaque psoriasis is less than 15%, according to a recently published analysis of data from the ClinicalTrials.gov database.

The exact figure drawn from the survey of 82 trials was 14.2%, but 20 (24%) of the trials did not include ethnoracial data at all, and only 65% of those with data had complete data, according to a report in the British Journal of Dermatology by a team of investigators from the department of dermatology at the University of California, San Francisco.

“The remaining studies reported the percentage of white participants only or white participants and one additional ethnoracial group,” reported the investigators, led by Vidhatha D. Reddy, a medical student at UCSF.

The investigators broke down participation by race in all phase 3 plaque psoriasis trials that enrolled adults and had posted results by May 2020. Data from trials of medications yet to be approved were excluded.

Most trials were multinational. The medications evaluated included 11 biologics, 10 topicals, 2 oral systemic agents, and a phosphodiesterase type-4 inhibitor. The 82 trials included in this analysis enrolled 48,846 collectively.

From trials that identified race, 85.8% of 39,161 participants were White, 3.09% of 25,565 patients were Black, 19.55% of 11,364 patients were Hispanic or Latino, and 9.21% of 30,009 patients were Asian. Of trials that included Native Americans or Pacific Islanders, fewer than 2% of participants represented this category.

Non-White patients remain underrepresented even when recognizing differences in the prevalence of psoriasis. For example, one recent survey found the U.S, prevalence of psoriasis to be about half as great in Blacks as it is in Whites (1.9% vs. 3.9%), but the representation of Blacks in the phase 3 trials evaluated by Mr. Reddy and colleagues was more than 20 times lower.

There are many reasons to suspect that lack of diversification in psoriasis trials is impeding optimal care in those underrepresented. Of several examples offered by the authors, one involved differential responses to adalimumab among patients with hidradenitis suppurativa with genetic variants in the BCL2 gene, but the authors reported racially associated genetic differences are not uncommon.

“Estimates have shown that approximately one-fifth of newly developed medications demonstrate interracial/ethnic variability in regard to various factors, such as pharmacokinetics, safety and efficacy profiles, dosing, and pharmacogenetics,” Mr. Reddy and his coinvestigators stated.

Although racial diversity in the design and recruitment for clinical trials has not been a priority in trials involving psoriasis, other skin diseases, or most diseases in general, the authors cited some evidence that this is changing.

“Since 2017, research funded by the National Institutes of Health has been required to report race and ethnicity of participants following an amendment to the Health Revitalization Act,” according to the authors, who suggested that other such initiatives are needed. They advocated “explicit goals to increase recruitment of people of color” as a standard step in clinical trial conduct.

Hypertension trials were cited as an example in which diversity has made a difference.

“Although Black patients are at an elevated risk of developing hypertension, it was not until the enrollment of a substantial proportion of black participants in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) that enough data on Black patients were available to make specific treatment recommendations in this population,” they noted.
 

Impossible to know treatment benefits without ethnoracial data

Penn Medicine

Another investigator who has considered this issue, Junko Takeshita, MD, PhD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, agreed.

“Lack of diversity among participants in phase 3 clinical trials for psoriasis is a problem,” said Dr. Takeshita, who led a study of racial differences in perceptions of psoriasis therapies that was published last year.

In that study, “my research group not only found differences in perceptions about biologics between Black and White patients with psoriasis, but we have also shown that Black patients with psoriasis are less likely to receive biologic treatment,” she reported. There are many explanations. For example, she found in another study that Black patients are underrepresented in direct-to-consumer advertisements for biologics.

This problem is not unique to psoriasis. Underrepresentation of Blacks and other ethnoracial groups is true of other skin diseases and many diseases in general, according to Dr. Takeshita. However, she cautioned that the 3% figure for Black participation in psoriasis trials reported by Mr. Reddy and colleagues is not necessarily reflective of trials in the United States.

“This study included international study sites that are recruiting patients from populations with different demographics than the U.S.,” she noted. By including sites with only Asian patients or countries with few Blacks in the population, it dilutes Black representation. She would expect the exact proportion of Black participants to be somewhat higher even if they are “still likely to be underrepresented” if the analysis has been limited to U.S. data.

The research had no funding source. Three of the nine authors reported financial relationships with pharmaceutical companies.

SOURCE: Reddy VD et al. Br J Dermatol. 2020 Sep 17. doi: 10.1111/bjd.19468.

Non-White patient participation in phase 3 therapeutic trials for plaque psoriasis is less than 15%, according to a recently published analysis of data from the ClinicalTrials.gov database.

The exact figure drawn from the survey of 82 trials was 14.2%, but 20 (24%) of the trials did not include ethnoracial data at all, and only 65% of those with data had complete data, according to a report in the British Journal of Dermatology by a team of investigators from the department of dermatology at the University of California, San Francisco.

“The remaining studies reported the percentage of white participants only or white participants and one additional ethnoracial group,” reported the investigators, led by Vidhatha D. Reddy, a medical student at UCSF.

The investigators broke down participation by race in all phase 3 plaque psoriasis trials that enrolled adults and had posted results by May 2020. Data from trials of medications yet to be approved were excluded.

Most trials were multinational. The medications evaluated included 11 biologics, 10 topicals, 2 oral systemic agents, and a phosphodiesterase type-4 inhibitor. The 82 trials included in this analysis enrolled 48,846 collectively.

From trials that identified race, 85.8% of 39,161 participants were White, 3.09% of 25,565 patients were Black, 19.55% of 11,364 patients were Hispanic or Latino, and 9.21% of 30,009 patients were Asian. Of trials that included Native Americans or Pacific Islanders, fewer than 2% of participants represented this category.

Non-White patients remain underrepresented even when recognizing differences in the prevalence of psoriasis. For example, one recent survey found the U.S, prevalence of psoriasis to be about half as great in Blacks as it is in Whites (1.9% vs. 3.9%), but the representation of Blacks in the phase 3 trials evaluated by Mr. Reddy and colleagues was more than 20 times lower.

There are many reasons to suspect that lack of diversification in psoriasis trials is impeding optimal care in those underrepresented. Of several examples offered by the authors, one involved differential responses to adalimumab among patients with hidradenitis suppurativa with genetic variants in the BCL2 gene, but the authors reported racially associated genetic differences are not uncommon.

“Estimates have shown that approximately one-fifth of newly developed medications demonstrate interracial/ethnic variability in regard to various factors, such as pharmacokinetics, safety and efficacy profiles, dosing, and pharmacogenetics,” Mr. Reddy and his coinvestigators stated.

Although racial diversity in the design and recruitment for clinical trials has not been a priority in trials involving psoriasis, other skin diseases, or most diseases in general, the authors cited some evidence that this is changing.

“Since 2017, research funded by the National Institutes of Health has been required to report race and ethnicity of participants following an amendment to the Health Revitalization Act,” according to the authors, who suggested that other such initiatives are needed. They advocated “explicit goals to increase recruitment of people of color” as a standard step in clinical trial conduct.

Hypertension trials were cited as an example in which diversity has made a difference.

“Although Black patients are at an elevated risk of developing hypertension, it was not until the enrollment of a substantial proportion of black participants in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) that enough data on Black patients were available to make specific treatment recommendations in this population,” they noted.
 

Impossible to know treatment benefits without ethnoracial data

Penn Medicine

Another investigator who has considered this issue, Junko Takeshita, MD, PhD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, agreed.

“Lack of diversity among participants in phase 3 clinical trials for psoriasis is a problem,” said Dr. Takeshita, who led a study of racial differences in perceptions of psoriasis therapies that was published last year.

In that study, “my research group not only found differences in perceptions about biologics between Black and White patients with psoriasis, but we have also shown that Black patients with psoriasis are less likely to receive biologic treatment,” she reported. There are many explanations. For example, she found in another study that Black patients are underrepresented in direct-to-consumer advertisements for biologics.

This problem is not unique to psoriasis. Underrepresentation of Blacks and other ethnoracial groups is true of other skin diseases and many diseases in general, according to Dr. Takeshita. However, she cautioned that the 3% figure for Black participation in psoriasis trials reported by Mr. Reddy and colleagues is not necessarily reflective of trials in the United States.

“This study included international study sites that are recruiting patients from populations with different demographics than the U.S.,” she noted. By including sites with only Asian patients or countries with few Blacks in the population, it dilutes Black representation. She would expect the exact proportion of Black participants to be somewhat higher even if they are “still likely to be underrepresented” if the analysis has been limited to U.S. data.

The research had no funding source. Three of the nine authors reported financial relationships with pharmaceutical companies.

SOURCE: Reddy VD et al. Br J Dermatol. 2020 Sep 17. doi: 10.1111/bjd.19468.

Non-White patient participation in phase 3 therapeutic trials for plaque psoriasis is less than 15%, according to a recently published analysis of data from the ClinicalTrials.gov database.

The exact figure drawn from the survey of 82 trials was 14.2%, but 20 (24%) of the trials did not include ethnoracial data at all, and only 65% of those with data had complete data, according to a report in the British Journal of Dermatology by a team of investigators from the department of dermatology at the University of California, San Francisco.

“The remaining studies reported the percentage of white participants only or white participants and one additional ethnoracial group,” reported the investigators, led by Vidhatha D. Reddy, a medical student at UCSF.

The investigators broke down participation by race in all phase 3 plaque psoriasis trials that enrolled adults and had posted results by May 2020. Data from trials of medications yet to be approved were excluded.

Most trials were multinational. The medications evaluated included 11 biologics, 10 topicals, 2 oral systemic agents, and a phosphodiesterase type-4 inhibitor. The 82 trials included in this analysis enrolled 48,846 collectively.

From trials that identified race, 85.8% of 39,161 participants were White, 3.09% of 25,565 patients were Black, 19.55% of 11,364 patients were Hispanic or Latino, and 9.21% of 30,009 patients were Asian. Of trials that included Native Americans or Pacific Islanders, fewer than 2% of participants represented this category.

Non-White patients remain underrepresented even when recognizing differences in the prevalence of psoriasis. For example, one recent survey found the U.S, prevalence of psoriasis to be about half as great in Blacks as it is in Whites (1.9% vs. 3.9%), but the representation of Blacks in the phase 3 trials evaluated by Mr. Reddy and colleagues was more than 20 times lower.

There are many reasons to suspect that lack of diversification in psoriasis trials is impeding optimal care in those underrepresented. Of several examples offered by the authors, one involved differential responses to adalimumab among patients with hidradenitis suppurativa with genetic variants in the BCL2 gene, but the authors reported racially associated genetic differences are not uncommon.

“Estimates have shown that approximately one-fifth of newly developed medications demonstrate interracial/ethnic variability in regard to various factors, such as pharmacokinetics, safety and efficacy profiles, dosing, and pharmacogenetics,” Mr. Reddy and his coinvestigators stated.

Although racial diversity in the design and recruitment for clinical trials has not been a priority in trials involving psoriasis, other skin diseases, or most diseases in general, the authors cited some evidence that this is changing.

“Since 2017, research funded by the National Institutes of Health has been required to report race and ethnicity of participants following an amendment to the Health Revitalization Act,” according to the authors, who suggested that other such initiatives are needed. They advocated “explicit goals to increase recruitment of people of color” as a standard step in clinical trial conduct.

Hypertension trials were cited as an example in which diversity has made a difference.

“Although Black patients are at an elevated risk of developing hypertension, it was not until the enrollment of a substantial proportion of black participants in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) that enough data on Black patients were available to make specific treatment recommendations in this population,” they noted.
 

Impossible to know treatment benefits without ethnoracial data

Penn Medicine

Another investigator who has considered this issue, Junko Takeshita, MD, PhD, an assistant professor of dermatology at the University of Pennsylvania, Philadelphia, agreed.

“Lack of diversity among participants in phase 3 clinical trials for psoriasis is a problem,” said Dr. Takeshita, who led a study of racial differences in perceptions of psoriasis therapies that was published last year.

In that study, “my research group not only found differences in perceptions about biologics between Black and White patients with psoriasis, but we have also shown that Black patients with psoriasis are less likely to receive biologic treatment,” she reported. There are many explanations. For example, she found in another study that Black patients are underrepresented in direct-to-consumer advertisements for biologics.

This problem is not unique to psoriasis. Underrepresentation of Blacks and other ethnoracial groups is true of other skin diseases and many diseases in general, according to Dr. Takeshita. However, she cautioned that the 3% figure for Black participation in psoriasis trials reported by Mr. Reddy and colleagues is not necessarily reflective of trials in the United States.

“This study included international study sites that are recruiting patients from populations with different demographics than the U.S.,” she noted. By including sites with only Asian patients or countries with few Blacks in the population, it dilutes Black representation. She would expect the exact proportion of Black participants to be somewhat higher even if they are “still likely to be underrepresented” if the analysis has been limited to U.S. data.

The research had no funding source. Three of the nine authors reported financial relationships with pharmaceutical companies.

SOURCE: Reddy VD et al. Br J Dermatol. 2020 Sep 17. doi: 10.1111/bjd.19468.

A 42-year-old woman with psoriasis presents for a checkup at the dermatology clinic. Her psoriasis has been fairly stable on methotrexate with no recent flares. She presents her concern of the coronavirus pandemic continuing into the flu season and mentions she would like to minimize her chances of having a respiratory illness. The influenza vaccine has just become available, and she inquires when she can get the vaccine and whether it will interfere with her treatment. What are your recommendations for the patient?

Psoriasis is an immune-mediated, inflammatory skin condition stemming from hyperproliferation of keratinocytes that classically involves erythematous skin plaques with overlying scale. Treatment options vary widely and include topical modalities, phototherapy, immunosuppressants, and biologic agents. Selection of treatment largely depends on the severity and extent of body surface area involvement; systemic therapy generally is indicated when the affected body surface area is greater than 5% to 10%. In patients on systemic therapy, increased susceptibility to infection is a priority concern for prescribing physicians. In the context of continuing immunosuppressive medications, vaccines that reduce susceptibility to infectious diseases can play an important role in reducing morbidity and mortality for these patients; however, an important consideration is that in patients with chronic conditions and frequent hospital visits, vaccines may be administered by various clinicians who may not be familiar with the management of immunosuppressive treatments. It is pivotal for prescribing dermatologists to provide appropriate vaccination instructions for the patient and any future clinicians to ensure vaccine efficacy in these patients.

The intramuscular influenza vaccine is a killed vaccine that is administered annually and has been shown to be safe for use in both immunocompetent and immunocompromised patients.^1,2 Despite its safety, questions remain regarding the efficacy of vaccines while a patient is unable to mount a normal immune response and whether the treatment must be altered to maximize immunogenicity. The common systemic treatment options for psoriasis and any recommendations that can be made regarding administration of the influenza vaccine in that context are outlined in the Table. Given the sparsity of clinical data measuring vaccine immunogenicity in patients with psoriasis, vaccine guidelines are drawn from patients with various conditions who are receiving the same dose of medication as indicated for psoriasis.

A 42-year-old woman with psoriasis presents for a checkup at the dermatology clinic. Her psoriasis has been fairly stable on methotrexate with no recent flares. She presents her concern of the coronavirus pandemic continuing into the flu season and mentions she would like to minimize her chances of having a respiratory illness. The influenza vaccine has just become available, and she inquires when she can get the vaccine and whether it will interfere with her treatment. What are your recommendations for the patient?

Psoriasis is an immune-mediated, inflammatory skin condition stemming from hyperproliferation of keratinocytes that classically involves erythematous skin plaques with overlying scale. Treatment options vary widely and include topical modalities, phototherapy, immunosuppressants, and biologic agents. Selection of treatment largely depends on the severity and extent of body surface area involvement; systemic therapy generally is indicated when the affected body surface area is greater than 5% to 10%. In patients on systemic therapy, increased susceptibility to infection is a priority concern for prescribing physicians. In the context of continuing immunosuppressive medications, vaccines that reduce susceptibility to infectious diseases can play an important role in reducing morbidity and mortality for these patients; however, an important consideration is that in patients with chronic conditions and frequent hospital visits, vaccines may be administered by various clinicians who may not be familiar with the management of immunosuppressive treatments. It is pivotal for prescribing dermatologists to provide appropriate vaccination instructions for the patient and any future clinicians to ensure vaccine efficacy in these patients.

The intramuscular influenza vaccine is a killed vaccine that is administered annually and has been shown to be safe for use in both immunocompetent and immunocompromised patients.^1,2 Despite its safety, questions remain regarding the efficacy of vaccines while a patient is unable to mount a normal immune response and whether the treatment must be altered to maximize immunogenicity. The common systemic treatment options for psoriasis and any recommendations that can be made regarding administration of the influenza vaccine in that context are outlined in the Table. Given the sparsity of clinical data measuring vaccine immunogenicity in patients with psoriasis, vaccine guidelines are drawn from patients with various conditions who are receiving the same dose of medication as indicated for psoriasis.

A 42-year-old woman with psoriasis presents for a checkup at the dermatology clinic. Her psoriasis has been fairly stable on methotrexate with no recent flares. She presents her concern of the coronavirus pandemic continuing into the flu season and mentions she would like to minimize her chances of having a respiratory illness. The influenza vaccine has just become available, and she inquires when she can get the vaccine and whether it will interfere with her treatment. What are your recommendations for the patient?

Psoriasis is an immune-mediated, inflammatory skin condition stemming from hyperproliferation of keratinocytes that classically involves erythematous skin plaques with overlying scale. Treatment options vary widely and include topical modalities, phototherapy, immunosuppressants, and biologic agents. Selection of treatment largely depends on the severity and extent of body surface area involvement; systemic therapy generally is indicated when the affected body surface area is greater than 5% to 10%. In patients on systemic therapy, increased susceptibility to infection is a priority concern for prescribing physicians. In the context of continuing immunosuppressive medications, vaccines that reduce susceptibility to infectious diseases can play an important role in reducing morbidity and mortality for these patients; however, an important consideration is that in patients with chronic conditions and frequent hospital visits, vaccines may be administered by various clinicians who may not be familiar with the management of immunosuppressive treatments. It is pivotal for prescribing dermatologists to provide appropriate vaccination instructions for the patient and any future clinicians to ensure vaccine efficacy in these patients.

The intramuscular influenza vaccine is a killed vaccine that is administered annually and has been shown to be safe for use in both immunocompetent and immunocompromised patients.^1,2 Despite its safety, questions remain regarding the efficacy of vaccines while a patient is unable to mount a normal immune response and whether the treatment must be altered to maximize immunogenicity. The common systemic treatment options for psoriasis and any recommendations that can be made regarding administration of the influenza vaccine in that context are outlined in the Table. Given the sparsity of clinical data measuring vaccine immunogenicity in patients with psoriasis, vaccine guidelines are drawn from patients with various conditions who are receiving the same dose of medication as indicated for psoriasis.

Psoriasis is a common chronic, multisystem, inflammatory disease with predominantly skin and joint manifestations that affects approximately 2% of the world’s population.¹ It occurs in a variety of clinical forms, from a few well-demarcated, erythematous plaques with a silvery scale to involvement of almost the entire body surface area. Beyond the debilitating physical ailments of the disease, psoriasis also may have psychosocial effects on quality of life.² The pathogenesis of psoriasis is not fully understood but represents a complex multifactorial disease with both immune-mediated and genetic components. Characterized by hyperplasia of epidermal keratinocytes, psoriasis is shown to be mediated by infiltration of T-cell lymphocytes with an increase of various inflammatory cytokines, including tumor necrosis factor (TNF) α.³ More recently, interactions of helper T cells (T_H17) via IL-17 and IL-23 have been supported to play a major role in the pathogenesis of psoriasis.^4,5

With the growing understanding of the pathophysiology of psoriasis, focused biologics have been developed to target specific cytokines implicated in the disease process and have been increasingly utilized. Tumor necrosis factor α inhibitors, including adalimumab, infliximab, and etanercept, along with the IL-12/IL-23 inhibitor ustekinumab, have been revolutionary in psoriasis treatment by providing safe and effective long-term therapy; however, there is concern of life-threatening infections with biologics because of the immunosuppressive effects and mechanisms of action.⁶ Specifically, there have been reported cases of deep fungal infections associated with TNF-α inhibitor use.⁷

Recently, the advent of IL-17 and IL-23 inhibitors has garnered notable interest in these biologics as promising treatments for psoriasis. With IL-17 and IL-23 supported to have a major role in the pathogenesis of psoriasis, targeting the cytokine is not only logical but also has proven to be effacacious.^8-10 Secukinumab, ixekizumab, and brodalumab are IL-17 inhibitors that have been approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis. Secukinumab and ixekizumab are anti–IL-17A monoclonal antibodies, whereas brodalumab is an anti–IL-17 receptor antibody. Risankizumab, guselkumab, and tildrakizumab are IL-23 inhibitors that also have been approved by the FDA for the treatment of psoriasis. As with older biologics, there is concern over the safety of these inhibitors because of the central role of IL-17 and IL-23 in both innate and adaptive immune responses, particularly against fungi.¹¹ Therefore, use of biologics targeting IL-17 and IL-23 may increase susceptibility to deep fungal infections.

Safety data and discussion of the risk for deep fungal infections from IL-17, IL-12/IL-23, and IL-23 inhibitor use for psoriasis treatment currently are lacking. Given the knowledge gap, we sought to synthesize and review the current evidence on risks for deep fungal infections during biologic therapy in patients with psoriasis, with a focus on IL-17 inhibitor therapies.

METHODS

A PubMed search of articles indexed for MEDLINE from database inception to 2019 (1946-2019) was performed to find randomized controlled trials (RCTs), including extended trials and clinical trials, for IL-17, IL-12/IL-23, and IL-23 inhibitors approved by the FDA for psoriasis treatment. The following keywords were used: psoriasis or inflammatory disease and secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, or tildrakizumab. Studies were restricted to the English-language literature, and those that did not provide adequate safety data on the specific types of infections that occurred were excluded.

RESULTSIL-17 Inhibitors

Our search yielded RCTs, some including extension trials, and clinical trials of IL-17 inhibitors used for psoriatic disease and other nonpsoriatic conditions (Table).

Risk for Deep Fungal Infection With Secukinumab
The queried studies included 20 RCTs or clinical trials along with extension trials of 3746 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 52 weeks. In a 3-year extension study of SCULPTURE, Bissonnette et al¹² reported no new safety concerns for the 340 patients with moderate to severe psoriasis treated with secukinumab. Common adverse events (AEs) included nasopharyngitis, upper respiratory tract infections, and headache, but there were no reports of deep fungal infections.¹² In a subsequent 5-year analysis of 168 patients that focused on the 300-mg fixed interval treatment with secukinumab, the safety profile remained favorable, with 0 reports of invasive fungal infections.¹³ A study (FEATURE) of 118 patients with psoriasis treated with a prefilled syringe of 300 or 150 mg of secukinumab also described an acceptable safety profile and reported no deep fungal infections.¹⁴ JUNCTURE, another study utilizing autoinjectors, also found that treatment with 300 or 150 mg of secukinumab was well tolerated in 121 patients, with no deep fungal infections.¹⁵ Common AEs for both studies included nasopharyngitis and headache.^14,15 A 24-week phase 3 study for scalp psoriasis treated with secukinumab also reported 0 deep fungal infections in 51 patients.¹⁶ In an RCT comparing secukinumab and ustekinumab for moderate to severe plaque psoriasis, Blauvelt et al¹⁷ demonstrated that the incidence of serious AEs was comparable between the 2 groups, with no reports of invasive fungal infections in the 334 patients exposed to secukinumab. The CLEAR study, which compared secukinumab and ustekinumab, also found no reported deep fungal disease in the 335 patients exposed to secukinumab.¹⁸ Secukinumab exhibited a similar safety profile to ustekinumab in both studies, with common AEs being headache and nasopharyngitis.^17,18 The GESTURE study investigated the efficacy of secukinumab in 137 patients with palmoplantar psoriasis and reported a favorable profile with no reports of deep fungal disease.¹⁹ In a subanalysis of the phase 3 study ERASURE, secukinumab was shown to have a robust and sustainable efficacy in 58 Japanese patients with moderate to severe plaque psoriasis, and there were no reports of invasive fungal infections.²⁰ Another subanalysis of 36 Taiwanese patients from the ERASURE study also had similar findings, with no dose relationship observed for AEs.²¹ In a phase 2 study of 103 patients with psoriasis, Papp et al²² demonstrated AE rates that were similar across different doses of secukinumab—3×150 mg, 3×75 mg, 3×25 mg, and 1×25 mg—and described no incidences of invasive fungal disease. In a phase 2 regimen-finding study of 337 patients conducted by Rich et al,²³ the most commonly reported AEs included nasopharyngitis, worsening psoriasis, and upper respiratory tract infections, but there were no reported deep fungal infections.

Our search also resulted in studies specific to the treatment of psoriatic arthritis (PsA) with secukinumab. McInnes et al⁹ conducted a phase 2 proof-of-concept trial for patients with PsA and reported no deep fungal infections in 28 patients exposed to 10 mg/kg of secukinumab. A 2-year follow-up with the cohort from FUTURE 1, a phase 3 clinical trial, also showed no new or unexpected safety signals in 404 patients exposed to 150 or 75 mg of secukinumab, including no reports of invasive fungal disease.²⁴ FUTURE 2, a phase 3 clinical trial, demonstrated that the most common AE was upper respiratory tract infection in the 299 patients treatedwith secukinumab, but there were no recorded invasive fungal infections.²⁵ In FUTURE 3, 277 patients were treated with secukinumab, with 14 nonserious candida infections but no observed deep fungal infections.²⁶ A study comparing secukinumab to fumaric acid esters reported that 6 of 105 patients treated with secukinumab also experienced superficial candidiasis, but there were no reports of deep fungal disease.²⁷

Secukinumab also has been used in the treatment of ankylosing spondylitis in a phase 3 RCT (MEASURE 1) in which 4 cases of superficial candidiasis were reported (0.7 cases per 100 patient-years of secukinumab) that were all resolved with standard antifungal therapy.²⁸ In MEASURE 2, a 5-year phase 3 RCT, 145 patients were treated with secukinumab for ankylosing spondylitis, with common AEs including nasopharyngitis, diarrhea, and upper respiratory tract infection, but there were no reports of any invasive fungal infections.²⁹ MEASURE 3 also demonstrated similar results in which no invasive fungal infections were observed.³⁰

Risk for Deep Fungal Infection With Ixekizumab
The queried studies included 7 RCTs or clinical trials of 3523 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 52 weeks. In UNCOVER-A, a phase 3 RCT of the pharmacokinetics and safety of ixekizumab, 204 patients were randomized to a prefilled syringe or autoinjector; 48% of patients experienced AEs, but no invasive fungal infections were observed.³¹ In an analysis of 3 phase 3 trials of ixekizumab including a total 2334 patients treated with ixekizumab from UNCOVER-1, UNCOVER-2, and UNCOVER-3, oral candidiasis frequently was reported, but no candidal infections met criteria for serious invasive infection.³² In UNCOVER-J, a 52-week phase 3 open-label trial of Japanese patients, 91 patients were treated for plaque psoriasis, erythrodermic psoriasis, or generalized pustular psoriasis using ixekizumab; the most common AEs included allergic reactions and injection-site reactions. One case of oral candidiasis was reported, but there were no reported cases of invasive fungal infections.³³ A comparison of ixekizumab vs ustekinumab from the IXORA-S trial demonstrated no substantial differences in AEs between the two, and no cases of deep fungal infections were reported. The most common AE between the 2 groups was nasopharyngitis.³⁴ An open-label extension over 4 years of a phase 2 RCT treated 211 patients with either 120 or 80 mg of ixekizumab; 87% of patients had experienced at least 1 AE, and all AEs were considered mild or moderate in severity, with no invasive fungal disease.³⁵

Our search also resulted in 1 study specific to the treatment of PsA with ixekizumab. A phase 3, 52-week study of patients treated with ixekizumab for PsA observed 2 incidences of oral candidiasis and nail candida infections, but no invasive fungal infections were reported.³⁶

We also found 1 study of ixekizumab used in the treatment of ankylosing spondylitis. COAST-V was a phase 3 RCT of patients treated for ankylosing spondylitis in which 164 patients were treated with ixekizumab; no serious AEs were recorded, including 0 deep fungal infections. The most common AEs observed were nasopharyngitis and upper respiratory tract infections.³⁷

Risk for Deep Fungal Infection With Brodalumab
The queried studies included 9 RCTs and 3 clinical trials along with extension trials of 1599 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 120 weeks. In a phase 2 RCT of Japanese patients with moderate to severe plaque psoriasis, 113 patients were treated with 70, 140, or 210 mg of brodalumab, and the most common AEs were nasopharyngitis, diarrhea, and upper respiratory tract inflammation. There were no reported cases of fungal infections in the study.³⁸ In an open-label extension study of Japanese patients that evaluated the long-term clinical safety of brodalumab, 145 patients were enrolled and observed similar AEs to the RCT, with 7 patients experiencing oral candidiasis and 1 patient having skin candidiasis, but there were no observed deep fungal infections.³⁹ In AMG 827, which evaluated the efficacy and safety of brodalumab, 320 patients were treated, and only 2 serious AEs were reported, neither of which were deep fungal disease.¹⁰ A phase 3 RCT conducted by Papp et al⁴⁰ (AMAGINE-1) also treated 441 patients with moderate to severe plaque psoriasis with brodalumab and observed candida infections in 9 patients that were mild to moderate and responsive to treatment, with no patients discontinuing the study. In a 120-week open-label extension study of 181 patients, Papp et al⁴¹ reported 8% of patients experienced serious AEs, with 1 case of latent tuberculosis that led to withdrawal of treatment. A study also investigated the efficacy and safety of brodalumab in 30 patients with generalized pustular psoriasis or psoriatic erythroderma and observed 2 cases of mild candida infections that resolved with treatment. There were no reports of invasive fungal disease.⁴²

Our search also resulted in studies of brodalumab used in the treatment of PsA and nonpsoriatic diseases. In one phase 2 RCT, 113 patients with PsA were treated with 140 mg, 280 mg, or combined doses of brodalumab, with the most common AEs being nasopharyngitis, upper respiratory tract infection, and diarrhea, but there were no reports of deep fungal infection.⁴³ In a phase 1b trial of patients with methotrexate-resistant rheumatoid arthritis treated with brodalumab, common AEs reported included headache, cough, and abdominal pain, with only 1 case of oral candidiasis that was determined not to be drug related.⁴⁴ Finally, an RCT of patients with moderate to severe asthma treated 226 patients with brodalumab and reported a greater incidence of oral candidiasis in treatment groups compared with placebo (3.5% vs 0%) but saw no instances of invasive fungal infection.⁴⁵

IL-12/IL-23 Inhibitor

Risk for Deep Fungal Infection With Ustekinumab
The queried studies included 4 RCTs of 954 patients with psoriasis treated with ustekinumab (eTable).^46-49 Within these trials, there were no reported cases of serious infections involving deep fungal organisms during the stated follow-up period. The literature search also found long-term safety data from the ACCEPT and PHOENIX trials that included 5437 patients with psoriasis treated with ustekinumab.^66,67 There also were no demonstrated incidences of invasive fungal disease in these studies, with most cases of infection being common bacterial or viral infections.

IL-23 Inhibitors

Risk for Deep Fungal Infection With Risankizumab, Guselkumab, and Tildrakizumab
The queried studies included 16 RCTs or clinical trials for psoriatic patients treated with IL-23 inhibitors, including 5 with risankizumab,^50-54 9 with guselkumab,^55-63 and 2 with tildrakizumab.^64,65 Within these trials there were no observed cases of serious infections with deep fungal disease.

COMMENT

Our literature review has demonstrated that there does not appear to be an increased incidence of deep fungal infections for patients treated with IL-17, IL-12/IL-23, or IL-23 inhibitors for psoriatic disease. All of the reviewed studies found no cases of invasive fungal infections for patients with psoriasis treated with secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, or tildrakizumab. Patients with other inflammatory conditions, such as ankylosing spondylitis, rheumatoid arthritis, and asthma, also did not appear to show an increased incidence of deep fungal disease.

Although these results show promising safety data for the use of these biologic therapies in treating inflammatory conditions, caution still is warranted, as these medications still are relatively new, with FDA approvals within the last 5 years. Safety data among different study populations also cannot be derived without further investigation, and much of the available literature is limited in long-term data. More extended trials or registry data from a large, broadly representative cohort are necessary to establish the long-term safety and risk for deep fungal infections with IL-17 and especially the newer IL-23 inhibitors.

A small percentage of patients from the reviewed literature did develop superficial candidiasis. This outcome can be expected, as the central role of IL-17 and IL-23 has been recognized in immunologic protection against infections, specifically against fungi.¹¹ Because all of the fungal infections reported for patients on IL-17 inhibitors were superficial candidiasis, guides for practical management and treatment should be implemented to standardize future research and care. A proposed screening algorithm for patients on these biologic therapies involves safety monitoring, including inspection of the oral cavity, folds, and genitals, along with inquiring about symptoms such as burning, dysgeusia, and dysuria.⁶⁸ If infection is suspected, confirmation by culture, molecular method, or optimally with esophagoscopy can be performed, and appropriate treatment may be initiated.⁶⁸ Patients with candida infections of the oral cavity, folds, or genitals can be placed on topical therapy such as nystatin, amphotericin B, ciclopirox, or other azoles, while those with infections of the esophagus can be started on oral fluconazole.⁶⁸

Although there were no reported cases of deep fungal infections, the theoretical risk for developing one while on IL-17 and IL-23 inhibitors may warrant further screening prior to beginning therapy. The TNF inhibitors approved for the treatment of psoriasis currently contain a black box warning for risk for disseminated and extrapulmonary histoplasmosis, coccidioidomycosis, blastomycosis, and other invasive fungal infections, which may highlight the importance of thorough evaluation and awareness of endemic areas for patients on biologics. Prior to initiating treatment with TNF inhibitors, current suggestions involve performing a thorough examination along with keeping a high index of suspicion for invasive fungal infections in patients who live in or have traveled to endemic regions.⁶⁹

Screening for invasive fungal infections for patients on TNF inhibitors involves questioning about potential exposures, such as demolition of old buildings, bird roosts, or spelunking.⁷⁰ Serologies or antigen testing can be used routinely, but as these tests are insensitive, empiric antifungal therapy should be initiated if there is high enough clinical suspicion.⁷¹ Currently, there are no clinical guidelines regarding fungal screening and initiation of IL-17 and IL-23 inhibitors for treatment of psoriasis and other inflammatory conditions, but careful stewardship over using these effective medications should still be practiced.

Upon review of the available safety data on the use of IL-17 and IL-23 inhibitors for the treatment of psoriasis and other inflammatory conditions, there does not appear to be an increased incidence of deep fungal infections. Physicians, however, should still be cautiously optimistic in prescribing these medications, as there is a theoretical risk for infection for all patients on biologics. A high index of suspicion for patients presenting with symptoms of fungal infections should be maintained, and appropriate diagnosis and management should be initiated if they do occur.

Psoriasis is a common chronic, multisystem, inflammatory disease with predominantly skin and joint manifestations that affects approximately 2% of the world’s population.¹ It occurs in a variety of clinical forms, from a few well-demarcated, erythematous plaques with a silvery scale to involvement of almost the entire body surface area. Beyond the debilitating physical ailments of the disease, psoriasis also may have psychosocial effects on quality of life.² The pathogenesis of psoriasis is not fully understood but represents a complex multifactorial disease with both immune-mediated and genetic components. Characterized by hyperplasia of epidermal keratinocytes, psoriasis is shown to be mediated by infiltration of T-cell lymphocytes with an increase of various inflammatory cytokines, including tumor necrosis factor (TNF) α.³ More recently, interactions of helper T cells (T_H17) via IL-17 and IL-23 have been supported to play a major role in the pathogenesis of psoriasis.^4,5

With the growing understanding of the pathophysiology of psoriasis, focused biologics have been developed to target specific cytokines implicated in the disease process and have been increasingly utilized. Tumor necrosis factor α inhibitors, including adalimumab, infliximab, and etanercept, along with the IL-12/IL-23 inhibitor ustekinumab, have been revolutionary in psoriasis treatment by providing safe and effective long-term therapy; however, there is concern of life-threatening infections with biologics because of the immunosuppressive effects and mechanisms of action.⁶ Specifically, there have been reported cases of deep fungal infections associated with TNF-α inhibitor use.⁷

Recently, the advent of IL-17 and IL-23 inhibitors has garnered notable interest in these biologics as promising treatments for psoriasis. With IL-17 and IL-23 supported to have a major role in the pathogenesis of psoriasis, targeting the cytokine is not only logical but also has proven to be effacacious.^8-10 Secukinumab, ixekizumab, and brodalumab are IL-17 inhibitors that have been approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis. Secukinumab and ixekizumab are anti–IL-17A monoclonal antibodies, whereas brodalumab is an anti–IL-17 receptor antibody. Risankizumab, guselkumab, and tildrakizumab are IL-23 inhibitors that also have been approved by the FDA for the treatment of psoriasis. As with older biologics, there is concern over the safety of these inhibitors because of the central role of IL-17 and IL-23 in both innate and adaptive immune responses, particularly against fungi.¹¹ Therefore, use of biologics targeting IL-17 and IL-23 may increase susceptibility to deep fungal infections.

Safety data and discussion of the risk for deep fungal infections from IL-17, IL-12/IL-23, and IL-23 inhibitor use for psoriasis treatment currently are lacking. Given the knowledge gap, we sought to synthesize and review the current evidence on risks for deep fungal infections during biologic therapy in patients with psoriasis, with a focus on IL-17 inhibitor therapies.

METHODS

A PubMed search of articles indexed for MEDLINE from database inception to 2019 (1946-2019) was performed to find randomized controlled trials (RCTs), including extended trials and clinical trials, for IL-17, IL-12/IL-23, and IL-23 inhibitors approved by the FDA for psoriasis treatment. The following keywords were used: psoriasis or inflammatory disease and secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, or tildrakizumab. Studies were restricted to the English-language literature, and those that did not provide adequate safety data on the specific types of infections that occurred were excluded.

RESULTSIL-17 Inhibitors

Our search yielded RCTs, some including extension trials, and clinical trials of IL-17 inhibitors used for psoriatic disease and other nonpsoriatic conditions (Table).

Risk for Deep Fungal Infection With Secukinumab
The queried studies included 20 RCTs or clinical trials along with extension trials of 3746 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 52 weeks. In a 3-year extension study of SCULPTURE, Bissonnette et al¹² reported no new safety concerns for the 340 patients with moderate to severe psoriasis treated with secukinumab. Common adverse events (AEs) included nasopharyngitis, upper respiratory tract infections, and headache, but there were no reports of deep fungal infections.¹² In a subsequent 5-year analysis of 168 patients that focused on the 300-mg fixed interval treatment with secukinumab, the safety profile remained favorable, with 0 reports of invasive fungal infections.¹³ A study (FEATURE) of 118 patients with psoriasis treated with a prefilled syringe of 300 or 150 mg of secukinumab also described an acceptable safety profile and reported no deep fungal infections.¹⁴ JUNCTURE, another study utilizing autoinjectors, also found that treatment with 300 or 150 mg of secukinumab was well tolerated in 121 patients, with no deep fungal infections.¹⁵ Common AEs for both studies included nasopharyngitis and headache.^14,15 A 24-week phase 3 study for scalp psoriasis treated with secukinumab also reported 0 deep fungal infections in 51 patients.¹⁶ In an RCT comparing secukinumab and ustekinumab for moderate to severe plaque psoriasis, Blauvelt et al¹⁷ demonstrated that the incidence of serious AEs was comparable between the 2 groups, with no reports of invasive fungal infections in the 334 patients exposed to secukinumab. The CLEAR study, which compared secukinumab and ustekinumab, also found no reported deep fungal disease in the 335 patients exposed to secukinumab.¹⁸ Secukinumab exhibited a similar safety profile to ustekinumab in both studies, with common AEs being headache and nasopharyngitis.^17,18 The GESTURE study investigated the efficacy of secukinumab in 137 patients with palmoplantar psoriasis and reported a favorable profile with no reports of deep fungal disease.¹⁹ In a subanalysis of the phase 3 study ERASURE, secukinumab was shown to have a robust and sustainable efficacy in 58 Japanese patients with moderate to severe plaque psoriasis, and there were no reports of invasive fungal infections.²⁰ Another subanalysis of 36 Taiwanese patients from the ERASURE study also had similar findings, with no dose relationship observed for AEs.²¹ In a phase 2 study of 103 patients with psoriasis, Papp et al²² demonstrated AE rates that were similar across different doses of secukinumab—3×150 mg, 3×75 mg, 3×25 mg, and 1×25 mg—and described no incidences of invasive fungal disease. In a phase 2 regimen-finding study of 337 patients conducted by Rich et al,²³ the most commonly reported AEs included nasopharyngitis, worsening psoriasis, and upper respiratory tract infections, but there were no reported deep fungal infections.

Our search also resulted in studies specific to the treatment of psoriatic arthritis (PsA) with secukinumab. McInnes et al⁹ conducted a phase 2 proof-of-concept trial for patients with PsA and reported no deep fungal infections in 28 patients exposed to 10 mg/kg of secukinumab. A 2-year follow-up with the cohort from FUTURE 1, a phase 3 clinical trial, also showed no new or unexpected safety signals in 404 patients exposed to 150 or 75 mg of secukinumab, including no reports of invasive fungal disease.²⁴ FUTURE 2, a phase 3 clinical trial, demonstrated that the most common AE was upper respiratory tract infection in the 299 patients treatedwith secukinumab, but there were no recorded invasive fungal infections.²⁵ In FUTURE 3, 277 patients were treated with secukinumab, with 14 nonserious candida infections but no observed deep fungal infections.²⁶ A study comparing secukinumab to fumaric acid esters reported that 6 of 105 patients treated with secukinumab also experienced superficial candidiasis, but there were no reports of deep fungal disease.²⁷

Secukinumab also has been used in the treatment of ankylosing spondylitis in a phase 3 RCT (MEASURE 1) in which 4 cases of superficial candidiasis were reported (0.7 cases per 100 patient-years of secukinumab) that were all resolved with standard antifungal therapy.²⁸ In MEASURE 2, a 5-year phase 3 RCT, 145 patients were treated with secukinumab for ankylosing spondylitis, with common AEs including nasopharyngitis, diarrhea, and upper respiratory tract infection, but there were no reports of any invasive fungal infections.²⁹ MEASURE 3 also demonstrated similar results in which no invasive fungal infections were observed.³⁰

Risk for Deep Fungal Infection With Ixekizumab
The queried studies included 7 RCTs or clinical trials of 3523 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 52 weeks. In UNCOVER-A, a phase 3 RCT of the pharmacokinetics and safety of ixekizumab, 204 patients were randomized to a prefilled syringe or autoinjector; 48% of patients experienced AEs, but no invasive fungal infections were observed.³¹ In an analysis of 3 phase 3 trials of ixekizumab including a total 2334 patients treated with ixekizumab from UNCOVER-1, UNCOVER-2, and UNCOVER-3, oral candidiasis frequently was reported, but no candidal infections met criteria for serious invasive infection.³² In UNCOVER-J, a 52-week phase 3 open-label trial of Japanese patients, 91 patients were treated for plaque psoriasis, erythrodermic psoriasis, or generalized pustular psoriasis using ixekizumab; the most common AEs included allergic reactions and injection-site reactions. One case of oral candidiasis was reported, but there were no reported cases of invasive fungal infections.³³ A comparison of ixekizumab vs ustekinumab from the IXORA-S trial demonstrated no substantial differences in AEs between the two, and no cases of deep fungal infections were reported. The most common AE between the 2 groups was nasopharyngitis.³⁴ An open-label extension over 4 years of a phase 2 RCT treated 211 patients with either 120 or 80 mg of ixekizumab; 87% of patients had experienced at least 1 AE, and all AEs were considered mild or moderate in severity, with no invasive fungal disease.³⁵

Our search also resulted in 1 study specific to the treatment of PsA with ixekizumab. A phase 3, 52-week study of patients treated with ixekizumab for PsA observed 2 incidences of oral candidiasis and nail candida infections, but no invasive fungal infections were reported.³⁶

We also found 1 study of ixekizumab used in the treatment of ankylosing spondylitis. COAST-V was a phase 3 RCT of patients treated for ankylosing spondylitis in which 164 patients were treated with ixekizumab; no serious AEs were recorded, including 0 deep fungal infections. The most common AEs observed were nasopharyngitis and upper respiratory tract infections.³⁷

Risk for Deep Fungal Infection With Brodalumab
The queried studies included 9 RCTs and 3 clinical trials along with extension trials of 1599 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 120 weeks. In a phase 2 RCT of Japanese patients with moderate to severe plaque psoriasis, 113 patients were treated with 70, 140, or 210 mg of brodalumab, and the most common AEs were nasopharyngitis, diarrhea, and upper respiratory tract inflammation. There were no reported cases of fungal infections in the study.³⁸ In an open-label extension study of Japanese patients that evaluated the long-term clinical safety of brodalumab, 145 patients were enrolled and observed similar AEs to the RCT, with 7 patients experiencing oral candidiasis and 1 patient having skin candidiasis, but there were no observed deep fungal infections.³⁹ In AMG 827, which evaluated the efficacy and safety of brodalumab, 320 patients were treated, and only 2 serious AEs were reported, neither of which were deep fungal disease.¹⁰ A phase 3 RCT conducted by Papp et al⁴⁰ (AMAGINE-1) also treated 441 patients with moderate to severe plaque psoriasis with brodalumab and observed candida infections in 9 patients that were mild to moderate and responsive to treatment, with no patients discontinuing the study. In a 120-week open-label extension study of 181 patients, Papp et al⁴¹ reported 8% of patients experienced serious AEs, with 1 case of latent tuberculosis that led to withdrawal of treatment. A study also investigated the efficacy and safety of brodalumab in 30 patients with generalized pustular psoriasis or psoriatic erythroderma and observed 2 cases of mild candida infections that resolved with treatment. There were no reports of invasive fungal disease.⁴²

Our search also resulted in studies of brodalumab used in the treatment of PsA and nonpsoriatic diseases. In one phase 2 RCT, 113 patients with PsA were treated with 140 mg, 280 mg, or combined doses of brodalumab, with the most common AEs being nasopharyngitis, upper respiratory tract infection, and diarrhea, but there were no reports of deep fungal infection.⁴³ In a phase 1b trial of patients with methotrexate-resistant rheumatoid arthritis treated with brodalumab, common AEs reported included headache, cough, and abdominal pain, with only 1 case of oral candidiasis that was determined not to be drug related.⁴⁴ Finally, an RCT of patients with moderate to severe asthma treated 226 patients with brodalumab and reported a greater incidence of oral candidiasis in treatment groups compared with placebo (3.5% vs 0%) but saw no instances of invasive fungal infection.⁴⁵

IL-12/IL-23 Inhibitor

Risk for Deep Fungal Infection With Ustekinumab
The queried studies included 4 RCTs of 954 patients with psoriasis treated with ustekinumab (eTable).^46-49 Within these trials, there were no reported cases of serious infections involving deep fungal organisms during the stated follow-up period. The literature search also found long-term safety data from the ACCEPT and PHOENIX trials that included 5437 patients with psoriasis treated with ustekinumab.^66,67 There also were no demonstrated incidences of invasive fungal disease in these studies, with most cases of infection being common bacterial or viral infections.

IL-23 Inhibitors

Risk for Deep Fungal Infection With Risankizumab, Guselkumab, and Tildrakizumab
The queried studies included 16 RCTs or clinical trials for psoriatic patients treated with IL-23 inhibitors, including 5 with risankizumab,^50-54 9 with guselkumab,^55-63 and 2 with tildrakizumab.^64,65 Within these trials there were no observed cases of serious infections with deep fungal disease.

COMMENT

Our literature review has demonstrated that there does not appear to be an increased incidence of deep fungal infections for patients treated with IL-17, IL-12/IL-23, or IL-23 inhibitors for psoriatic disease. All of the reviewed studies found no cases of invasive fungal infections for patients with psoriasis treated with secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, or tildrakizumab. Patients with other inflammatory conditions, such as ankylosing spondylitis, rheumatoid arthritis, and asthma, also did not appear to show an increased incidence of deep fungal disease.

Although these results show promising safety data for the use of these biologic therapies in treating inflammatory conditions, caution still is warranted, as these medications still are relatively new, with FDA approvals within the last 5 years. Safety data among different study populations also cannot be derived without further investigation, and much of the available literature is limited in long-term data. More extended trials or registry data from a large, broadly representative cohort are necessary to establish the long-term safety and risk for deep fungal infections with IL-17 and especially the newer IL-23 inhibitors.

A small percentage of patients from the reviewed literature did develop superficial candidiasis. This outcome can be expected, as the central role of IL-17 and IL-23 has been recognized in immunologic protection against infections, specifically against fungi.¹¹ Because all of the fungal infections reported for patients on IL-17 inhibitors were superficial candidiasis, guides for practical management and treatment should be implemented to standardize future research and care. A proposed screening algorithm for patients on these biologic therapies involves safety monitoring, including inspection of the oral cavity, folds, and genitals, along with inquiring about symptoms such as burning, dysgeusia, and dysuria.⁶⁸ If infection is suspected, confirmation by culture, molecular method, or optimally with esophagoscopy can be performed, and appropriate treatment may be initiated.⁶⁸ Patients with candida infections of the oral cavity, folds, or genitals can be placed on topical therapy such as nystatin, amphotericin B, ciclopirox, or other azoles, while those with infections of the esophagus can be started on oral fluconazole.⁶⁸

Although there were no reported cases of deep fungal infections, the theoretical risk for developing one while on IL-17 and IL-23 inhibitors may warrant further screening prior to beginning therapy. The TNF inhibitors approved for the treatment of psoriasis currently contain a black box warning for risk for disseminated and extrapulmonary histoplasmosis, coccidioidomycosis, blastomycosis, and other invasive fungal infections, which may highlight the importance of thorough evaluation and awareness of endemic areas for patients on biologics. Prior to initiating treatment with TNF inhibitors, current suggestions involve performing a thorough examination along with keeping a high index of suspicion for invasive fungal infections in patients who live in or have traveled to endemic regions.⁶⁹

Screening for invasive fungal infections for patients on TNF inhibitors involves questioning about potential exposures, such as demolition of old buildings, bird roosts, or spelunking.⁷⁰ Serologies or antigen testing can be used routinely, but as these tests are insensitive, empiric antifungal therapy should be initiated if there is high enough clinical suspicion.⁷¹ Currently, there are no clinical guidelines regarding fungal screening and initiation of IL-17 and IL-23 inhibitors for treatment of psoriasis and other inflammatory conditions, but careful stewardship over using these effective medications should still be practiced.

Upon review of the available safety data on the use of IL-17 and IL-23 inhibitors for the treatment of psoriasis and other inflammatory conditions, there does not appear to be an increased incidence of deep fungal infections. Physicians, however, should still be cautiously optimistic in prescribing these medications, as there is a theoretical risk for infection for all patients on biologics. A high index of suspicion for patients presenting with symptoms of fungal infections should be maintained, and appropriate diagnosis and management should be initiated if they do occur.

Psoriasis is a common chronic, multisystem, inflammatory disease with predominantly skin and joint manifestations that affects approximately 2% of the world’s population.¹ It occurs in a variety of clinical forms, from a few well-demarcated, erythematous plaques with a silvery scale to involvement of almost the entire body surface area. Beyond the debilitating physical ailments of the disease, psoriasis also may have psychosocial effects on quality of life.² The pathogenesis of psoriasis is not fully understood but represents a complex multifactorial disease with both immune-mediated and genetic components. Characterized by hyperplasia of epidermal keratinocytes, psoriasis is shown to be mediated by infiltration of T-cell lymphocytes with an increase of various inflammatory cytokines, including tumor necrosis factor (TNF) α.³ More recently, interactions of helper T cells (T_H17) via IL-17 and IL-23 have been supported to play a major role in the pathogenesis of psoriasis.^4,5

With the growing understanding of the pathophysiology of psoriasis, focused biologics have been developed to target specific cytokines implicated in the disease process and have been increasingly utilized. Tumor necrosis factor α inhibitors, including adalimumab, infliximab, and etanercept, along with the IL-12/IL-23 inhibitor ustekinumab, have been revolutionary in psoriasis treatment by providing safe and effective long-term therapy; however, there is concern of life-threatening infections with biologics because of the immunosuppressive effects and mechanisms of action.⁶ Specifically, there have been reported cases of deep fungal infections associated with TNF-α inhibitor use.⁷

Recently, the advent of IL-17 and IL-23 inhibitors has garnered notable interest in these biologics as promising treatments for psoriasis. With IL-17 and IL-23 supported to have a major role in the pathogenesis of psoriasis, targeting the cytokine is not only logical but also has proven to be effacacious.^8-10 Secukinumab, ixekizumab, and brodalumab are IL-17 inhibitors that have been approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis. Secukinumab and ixekizumab are anti–IL-17A monoclonal antibodies, whereas brodalumab is an anti–IL-17 receptor antibody. Risankizumab, guselkumab, and tildrakizumab are IL-23 inhibitors that also have been approved by the FDA for the treatment of psoriasis. As with older biologics, there is concern over the safety of these inhibitors because of the central role of IL-17 and IL-23 in both innate and adaptive immune responses, particularly against fungi.¹¹ Therefore, use of biologics targeting IL-17 and IL-23 may increase susceptibility to deep fungal infections.

Safety data and discussion of the risk for deep fungal infections from IL-17, IL-12/IL-23, and IL-23 inhibitor use for psoriasis treatment currently are lacking. Given the knowledge gap, we sought to synthesize and review the current evidence on risks for deep fungal infections during biologic therapy in patients with psoriasis, with a focus on IL-17 inhibitor therapies.

METHODS

A PubMed search of articles indexed for MEDLINE from database inception to 2019 (1946-2019) was performed to find randomized controlled trials (RCTs), including extended trials and clinical trials, for IL-17, IL-12/IL-23, and IL-23 inhibitors approved by the FDA for psoriasis treatment. The following keywords were used: psoriasis or inflammatory disease and secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, or tildrakizumab. Studies were restricted to the English-language literature, and those that did not provide adequate safety data on the specific types of infections that occurred were excluded.

RESULTSIL-17 Inhibitors

Our search yielded RCTs, some including extension trials, and clinical trials of IL-17 inhibitors used for psoriatic disease and other nonpsoriatic conditions (Table).

Risk for Deep Fungal Infection With Secukinumab
The queried studies included 20 RCTs or clinical trials along with extension trials of 3746 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 52 weeks. In a 3-year extension study of SCULPTURE, Bissonnette et al¹² reported no new safety concerns for the 340 patients with moderate to severe psoriasis treated with secukinumab. Common adverse events (AEs) included nasopharyngitis, upper respiratory tract infections, and headache, but there were no reports of deep fungal infections.¹² In a subsequent 5-year analysis of 168 patients that focused on the 300-mg fixed interval treatment with secukinumab, the safety profile remained favorable, with 0 reports of invasive fungal infections.¹³ A study (FEATURE) of 118 patients with psoriasis treated with a prefilled syringe of 300 or 150 mg of secukinumab also described an acceptable safety profile and reported no deep fungal infections.¹⁴ JUNCTURE, another study utilizing autoinjectors, also found that treatment with 300 or 150 mg of secukinumab was well tolerated in 121 patients, with no deep fungal infections.¹⁵ Common AEs for both studies included nasopharyngitis and headache.^14,15 A 24-week phase 3 study for scalp psoriasis treated with secukinumab also reported 0 deep fungal infections in 51 patients.¹⁶ In an RCT comparing secukinumab and ustekinumab for moderate to severe plaque psoriasis, Blauvelt et al¹⁷ demonstrated that the incidence of serious AEs was comparable between the 2 groups, with no reports of invasive fungal infections in the 334 patients exposed to secukinumab. The CLEAR study, which compared secukinumab and ustekinumab, also found no reported deep fungal disease in the 335 patients exposed to secukinumab.¹⁸ Secukinumab exhibited a similar safety profile to ustekinumab in both studies, with common AEs being headache and nasopharyngitis.^17,18 The GESTURE study investigated the efficacy of secukinumab in 137 patients with palmoplantar psoriasis and reported a favorable profile with no reports of deep fungal disease.¹⁹ In a subanalysis of the phase 3 study ERASURE, secukinumab was shown to have a robust and sustainable efficacy in 58 Japanese patients with moderate to severe plaque psoriasis, and there were no reports of invasive fungal infections.²⁰ Another subanalysis of 36 Taiwanese patients from the ERASURE study also had similar findings, with no dose relationship observed for AEs.²¹ In a phase 2 study of 103 patients with psoriasis, Papp et al²² demonstrated AE rates that were similar across different doses of secukinumab—3×150 mg, 3×75 mg, 3×25 mg, and 1×25 mg—and described no incidences of invasive fungal disease. In a phase 2 regimen-finding study of 337 patients conducted by Rich et al,²³ the most commonly reported AEs included nasopharyngitis, worsening psoriasis, and upper respiratory tract infections, but there were no reported deep fungal infections.

Our search also resulted in studies specific to the treatment of psoriatic arthritis (PsA) with secukinumab. McInnes et al⁹ conducted a phase 2 proof-of-concept trial for patients with PsA and reported no deep fungal infections in 28 patients exposed to 10 mg/kg of secukinumab. A 2-year follow-up with the cohort from FUTURE 1, a phase 3 clinical trial, also showed no new or unexpected safety signals in 404 patients exposed to 150 or 75 mg of secukinumab, including no reports of invasive fungal disease.²⁴ FUTURE 2, a phase 3 clinical trial, demonstrated that the most common AE was upper respiratory tract infection in the 299 patients treatedwith secukinumab, but there were no recorded invasive fungal infections.²⁵ In FUTURE 3, 277 patients were treated with secukinumab, with 14 nonserious candida infections but no observed deep fungal infections.²⁶ A study comparing secukinumab to fumaric acid esters reported that 6 of 105 patients treated with secukinumab also experienced superficial candidiasis, but there were no reports of deep fungal disease.²⁷

Secukinumab also has been used in the treatment of ankylosing spondylitis in a phase 3 RCT (MEASURE 1) in which 4 cases of superficial candidiasis were reported (0.7 cases per 100 patient-years of secukinumab) that were all resolved with standard antifungal therapy.²⁸ In MEASURE 2, a 5-year phase 3 RCT, 145 patients were treated with secukinumab for ankylosing spondylitis, with common AEs including nasopharyngitis, diarrhea, and upper respiratory tract infection, but there were no reports of any invasive fungal infections.²⁹ MEASURE 3 also demonstrated similar results in which no invasive fungal infections were observed.³⁰

Risk for Deep Fungal Infection With Ixekizumab
The queried studies included 7 RCTs or clinical trials of 3523 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 52 weeks. In UNCOVER-A, a phase 3 RCT of the pharmacokinetics and safety of ixekizumab, 204 patients were randomized to a prefilled syringe or autoinjector; 48% of patients experienced AEs, but no invasive fungal infections were observed.³¹ In an analysis of 3 phase 3 trials of ixekizumab including a total 2334 patients treated with ixekizumab from UNCOVER-1, UNCOVER-2, and UNCOVER-3, oral candidiasis frequently was reported, but no candidal infections met criteria for serious invasive infection.³² In UNCOVER-J, a 52-week phase 3 open-label trial of Japanese patients, 91 patients were treated for plaque psoriasis, erythrodermic psoriasis, or generalized pustular psoriasis using ixekizumab; the most common AEs included allergic reactions and injection-site reactions. One case of oral candidiasis was reported, but there were no reported cases of invasive fungal infections.³³ A comparison of ixekizumab vs ustekinumab from the IXORA-S trial demonstrated no substantial differences in AEs between the two, and no cases of deep fungal infections were reported. The most common AE between the 2 groups was nasopharyngitis.³⁴ An open-label extension over 4 years of a phase 2 RCT treated 211 patients with either 120 or 80 mg of ixekizumab; 87% of patients had experienced at least 1 AE, and all AEs were considered mild or moderate in severity, with no invasive fungal disease.³⁵

Our search also resulted in 1 study specific to the treatment of PsA with ixekizumab. A phase 3, 52-week study of patients treated with ixekizumab for PsA observed 2 incidences of oral candidiasis and nail candida infections, but no invasive fungal infections were reported.³⁶

We also found 1 study of ixekizumab used in the treatment of ankylosing spondylitis. COAST-V was a phase 3 RCT of patients treated for ankylosing spondylitis in which 164 patients were treated with ixekizumab; no serious AEs were recorded, including 0 deep fungal infections. The most common AEs observed were nasopharyngitis and upper respiratory tract infections.³⁷

Risk for Deep Fungal Infection With Brodalumab
The queried studies included 9 RCTs and 3 clinical trials along with extension trials of 1599 patients with psoriasis or other inflammatory conditions, with follow-up ranging from 12 to 120 weeks. In a phase 2 RCT of Japanese patients with moderate to severe plaque psoriasis, 113 patients were treated with 70, 140, or 210 mg of brodalumab, and the most common AEs were nasopharyngitis, diarrhea, and upper respiratory tract inflammation. There were no reported cases of fungal infections in the study.³⁸ In an open-label extension study of Japanese patients that evaluated the long-term clinical safety of brodalumab, 145 patients were enrolled and observed similar AEs to the RCT, with 7 patients experiencing oral candidiasis and 1 patient having skin candidiasis, but there were no observed deep fungal infections.³⁹ In AMG 827, which evaluated the efficacy and safety of brodalumab, 320 patients were treated, and only 2 serious AEs were reported, neither of which were deep fungal disease.¹⁰ A phase 3 RCT conducted by Papp et al⁴⁰ (AMAGINE-1) also treated 441 patients with moderate to severe plaque psoriasis with brodalumab and observed candida infections in 9 patients that were mild to moderate and responsive to treatment, with no patients discontinuing the study. In a 120-week open-label extension study of 181 patients, Papp et al⁴¹ reported 8% of patients experienced serious AEs, with 1 case of latent tuberculosis that led to withdrawal of treatment. A study also investigated the efficacy and safety of brodalumab in 30 patients with generalized pustular psoriasis or psoriatic erythroderma and observed 2 cases of mild candida infections that resolved with treatment. There were no reports of invasive fungal disease.⁴²

Our search also resulted in studies of brodalumab used in the treatment of PsA and nonpsoriatic diseases. In one phase 2 RCT, 113 patients with PsA were treated with 140 mg, 280 mg, or combined doses of brodalumab, with the most common AEs being nasopharyngitis, upper respiratory tract infection, and diarrhea, but there were no reports of deep fungal infection.⁴³ In a phase 1b trial of patients with methotrexate-resistant rheumatoid arthritis treated with brodalumab, common AEs reported included headache, cough, and abdominal pain, with only 1 case of oral candidiasis that was determined not to be drug related.⁴⁴ Finally, an RCT of patients with moderate to severe asthma treated 226 patients with brodalumab and reported a greater incidence of oral candidiasis in treatment groups compared with placebo (3.5% vs 0%) but saw no instances of invasive fungal infection.⁴⁵

IL-12/IL-23 Inhibitor

Risk for Deep Fungal Infection With Ustekinumab
The queried studies included 4 RCTs of 954 patients with psoriasis treated with ustekinumab (eTable).^46-49 Within these trials, there were no reported cases of serious infections involving deep fungal organisms during the stated follow-up period. The literature search also found long-term safety data from the ACCEPT and PHOENIX trials that included 5437 patients with psoriasis treated with ustekinumab.^66,67 There also were no demonstrated incidences of invasive fungal disease in these studies, with most cases of infection being common bacterial or viral infections.

IL-23 Inhibitors

Risk for Deep Fungal Infection With Risankizumab, Guselkumab, and Tildrakizumab
The queried studies included 16 RCTs or clinical trials for psoriatic patients treated with IL-23 inhibitors, including 5 with risankizumab,^50-54 9 with guselkumab,^55-63 and 2 with tildrakizumab.^64,65 Within these trials there were no observed cases of serious infections with deep fungal disease.

COMMENT

Our literature review has demonstrated that there does not appear to be an increased incidence of deep fungal infections for patients treated with IL-17, IL-12/IL-23, or IL-23 inhibitors for psoriatic disease. All of the reviewed studies found no cases of invasive fungal infections for patients with psoriasis treated with secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, or tildrakizumab. Patients with other inflammatory conditions, such as ankylosing spondylitis, rheumatoid arthritis, and asthma, also did not appear to show an increased incidence of deep fungal disease.

Although these results show promising safety data for the use of these biologic therapies in treating inflammatory conditions, caution still is warranted, as these medications still are relatively new, with FDA approvals within the last 5 years. Safety data among different study populations also cannot be derived without further investigation, and much of the available literature is limited in long-term data. More extended trials or registry data from a large, broadly representative cohort are necessary to establish the long-term safety and risk for deep fungal infections with IL-17 and especially the newer IL-23 inhibitors.

A small percentage of patients from the reviewed literature did develop superficial candidiasis. This outcome can be expected, as the central role of IL-17 and IL-23 has been recognized in immunologic protection against infections, specifically against fungi.¹¹ Because all of the fungal infections reported for patients on IL-17 inhibitors were superficial candidiasis, guides for practical management and treatment should be implemented to standardize future research and care. A proposed screening algorithm for patients on these biologic therapies involves safety monitoring, including inspection of the oral cavity, folds, and genitals, along with inquiring about symptoms such as burning, dysgeusia, and dysuria.⁶⁸ If infection is suspected, confirmation by culture, molecular method, or optimally with esophagoscopy can be performed, and appropriate treatment may be initiated.⁶⁸ Patients with candida infections of the oral cavity, folds, or genitals can be placed on topical therapy such as nystatin, amphotericin B, ciclopirox, or other azoles, while those with infections of the esophagus can be started on oral fluconazole.⁶⁸

Although there were no reported cases of deep fungal infections, the theoretical risk for developing one while on IL-17 and IL-23 inhibitors may warrant further screening prior to beginning therapy. The TNF inhibitors approved for the treatment of psoriasis currently contain a black box warning for risk for disseminated and extrapulmonary histoplasmosis, coccidioidomycosis, blastomycosis, and other invasive fungal infections, which may highlight the importance of thorough evaluation and awareness of endemic areas for patients on biologics. Prior to initiating treatment with TNF inhibitors, current suggestions involve performing a thorough examination along with keeping a high index of suspicion for invasive fungal infections in patients who live in or have traveled to endemic regions.⁶⁹

Screening for invasive fungal infections for patients on TNF inhibitors involves questioning about potential exposures, such as demolition of old buildings, bird roosts, or spelunking.⁷⁰ Serologies or antigen testing can be used routinely, but as these tests are insensitive, empiric antifungal therapy should be initiated if there is high enough clinical suspicion.⁷¹ Currently, there are no clinical guidelines regarding fungal screening and initiation of IL-17 and IL-23 inhibitors for treatment of psoriasis and other inflammatory conditions, but careful stewardship over using these effective medications should still be practiced.

Upon review of the available safety data on the use of IL-17 and IL-23 inhibitors for the treatment of psoriasis and other inflammatory conditions, there does not appear to be an increased incidence of deep fungal infections. Physicians, however, should still be cautiously optimistic in prescribing these medications, as there is a theoretical risk for infection for all patients on biologics. A high index of suspicion for patients presenting with symptoms of fungal infections should be maintained, and appropriate diagnosis and management should be initiated if they do occur.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.