Jonathan Silverberg, MD, PhD, MPH

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

Atopic dermatitis can really mess with patients’ lives

Atopic dermatitis (AD) is a multi-faceted disease that can cause major burden to the lives of patients. Chronic itch is the most common and burdensome symptom of AD and can be very distressing and debilitating for patients.¹Visible skin lesions of AD can be embarrassing and contribute to decreased self-esteem and psychosocial distress (ref). Recent studies uncovered many additional impacts and sequelae of AD.

• While itch has been long recognized as a burdensome symptom in AD, skin pain was recently shown to be an important symptom of AD. Cheng et al² performed a cross-sectional national survey of 240 children with AD and their parents, of which 200 had moderate-to-very severe disease. They found that skin pain intensity was associated with increased skin bleeding (adjusted β [95% CI]: 1.47 [0.61-2.33]), weeping/oozing (adjusted β [95% CI]: 1.18 [0.47-1.90]), and cracking (adjusted β [95% CI]: 1.00 [0.27-1.73]). These relationships may be indirectly related to scratching of the skin leading to open sores that hurt but also bleed, weep/ooze, and crack. On the other hand, patients may experience cracking of skin on hands and feet secondary to dryness and inflammation that can cause skin pain. The authors also found that parent-reported pain intensity was associated with impaired quality of life in infants aged 1-4 years (adjusted β [95% CI]: 1.16 [0.18-2.14]) and children aged 5-17 years (adjusted β [95% CI]: 1.68 [1.00-2.36]). These results show that skin pain is a burdensome symptom in children and adolescents with AD.

• Sleep disturbance is a major problem in patients with AD, especially in those with moderate-to-severe AD. Zhou et al³ conducted a cross-sectional study of 60 children aged 1-4 years with mild-to-severe AD. They found that eczema caused sleep disturbance on 5 or more nights in the past week in 76% of children with severe AD, 24% children with moderate AD, but none with mild AD. Children with more severe AD had greater attention dysregulation (correlation coefficient 0.65). AD severity was a significant predictor of both poor sleep health (β = 0.79) and attention dysregulation (β = 1.22). These results have important ramifications for pediatric health. Previous studies found associations of AD with attention-deficit disorder and attention-deficit hyperactivity disorder. The results of Zhou et al. suggest that AD is associated with symptoms of attention dysregulation, likely secondary to distraction from itch, chronic sleep deprivation, skin pain, etc.

• AD can affect individuals of all age groups, though there may be distinct ramifications when this debilitating disease occurs in childhood during the formative years of life. Manjunath et al⁴ examined data from the Fragile Families and Child Wellbeing Study, which is a prospective, longitudinal birth cohort including 4,898 children aged 1, 3, 5, 9, or 15 years. They found that AD in children aged 5 years (adjusted odds ratio [aOR] [95% CI]: 1.31 [1.04-1.64]) or 9 years (aOR [95% CI]: 1.38 [1.14-1.67]) was associated with ≥75th percentile of mean delinquent behavior scores at age 9 or 15 years. At 9 years of age, a 1-year history of AD was associated with smoking at age 15 years (aOR [95% CI]: 1.46 [1.00-2.13]), damaging property (aOR [95% CI]: 1.38 [1.08-1.77]), cheating on a test (aOR [95% CI]: 1.62 [1.17-2.26]), and school suspension (aOR [95% CI]: 1.36 [1.08-1.71]). These results are provocative and suggest that AD negatively impacts children’s behavior. This study was not able to examine specific clinical aspects of AD that led to delinquent behaviors. However, it is likely that multiple factors contribute to this association, including chronic itch, skin pain, sleep deprivation, attention dysregulation, psychosocial distress, teasing, and bullying.

• A major question on everyone’s mind these days is which individuals have a higher risk of developing COVID-19 infections. There have been many studies since the pandemic began on whether specific immune-mediated disorders are associated with higher risk of COVID-19 or worse outcomes from COVID-19 infections. Previous studies found mixed results about whether individuals with AD have higher risk of COVID-19. Fan et al⁵ performed a case-control study from a large healthcare system database, including 11,752 patients with AD and 47,008 age, sex and race matched healthy controls. They found that patients with AD were more likely to have a diagnosis of COVID-19 compared to those without AD (4.2% vs. 2.8%; P < .001). This association remained significant even after adjusting for demographic factors and comorbidities (odds ratio 1.29; P < .001). Of note, the effect-size was relatively modest in multivariable models. Residual confounding always remains a possibility, ie, that there are other unexplained factors in common with COVID-19 and AD that explain the association. Nevertheless, the results raise important questions about whether immune dysregulation or different treatments used in AD increase risk of COVID-19. Future studies are certainly warranted. Better yet, I look forward to the end of the pandemic when we will no longer have to worry about the potential harms of COVID-19 on AD patients.

References

1. Kim BS. Atopic Dermatitis Clinical Presentation. Medscape (Jan 10, 2022). https://emedicine.medscape.com/article/1049085-clinical (accessed Jan 28, 2022).
2. Cheng BT et al. Burden and characteristics of skin pain among children with atopic dermatitis. J Allergy Clin Immunol Pract. 2021 (Dec 23).
3. Zhou et al. Parent report of sleep health and attention regulation in a cross-sectional study of infants and preschool-aged children with atopic dermatitis. Pediatr Dermatol. 2021 (Dec 21).
4. Manjunath et al. Association of atopic dermatitis with delinquent behaviors in US children and adolescents. Arch Dermatol Res. 2022 (Jan 10).
5. Fan et al. Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program. JAAD Int. 2021;6:P77-81 (Dec 27).

A new era of evidence-based practice for atopic dermatitis

Atopic dermatitis (AD) is one of the most common diseases of childhood and still very common in adults worldwide. AD is also a very burdensome disease with considerable patient-burden. Despite the enormous population- and patient- burden, there remain many unmet needs in the management of AD. In addition, many treatments commonly used in AD had scant or mixed evidence regarding their efficacy and safety. For example, topical corticosteroids (TCS) are the workhorse for treatment in AD and most other inflammatory skin diseases. Yet, virtually everything we know about the efficacy of TCS comes from vasoconstriction proxy assays with almost no studies formally studying the efficacy of TCS in AD. Similarly, many therapies used off-label to treat more severe AD, such as phototherapy or allergen immunotherapy have inconsistent evidence to guide their use. Well, things are finally changing and the evidence is coming in at a frenzied pace. Development of multiple novel therapeutics in AD led to renewed interest in studying the efficacy and safety of older therapies as well.

• Phototherapy is an important treatment modality in AD patients who have an inadequate response to topical therapy. Many different modalities and devices were used to treat AD over the years, including narrowband ultraviolet B (NBUVB) and ultraviolet A (UVA)-1. NBUVB is the most commonly used approach in the United States and some other regions of the world. Ben Mordehai et al. published the results of a retrospective cohort study of 390 Israeli patients with moderate-severe AD treated with NBUVB therapy between 2000-2017 with ≥3 years of follow-up. Overall, 55.4% achieved an Investigator’s Global Assessment score of clear or almost clear. Facial involvement, occurrence of adverse effects, fewer treatments, and pretreatment immunoglobulin E levels >4000 IU/ml were associated with poorer clinical response to NBUVB. Median duration of response was 12 months with more relapses in children (<18 years).

• House dust mites (HDM) were previously shown to be triggers of AD via Immunoglobulin E dependent and independent mechanisms. Unfortunately, HDM avoidance is challenging for patients and has not proven to be reliably effective in clinical trials. Previous studies examined different approaches for immunotherapy to HDM with mixed results. Langer et al. published the results of a randomized, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT) or placebo for 18 months in 91 children and adults with AD and positive skin test result and/or Immunoglobulin E to Dermatophagoides pteronyssinus. After 18 months, patients treated with HDM SLIT achieved greater reductions in the SCOring AD (SCORAD) index and were more likely to achieve an Investigator’s Global Assessment score of clear or almost clear compared to placebo. Headache and abdominal pain were the most common adverse events reported by both groups. Efficacy of HDM SLIT in this study was relatively modest. Nevertheless, it appears to be a safe therapy and a reasonable adjunctive therapy in patients with AD whose disease is believed to be triggered by HDM.

• We are fortunate to have multiple non-steroidal topical therapies for atopic dermatitis, including crisaborole ointment, pimecrolimus cream and tacrolimus ointment. A number of questions remain about how these therapies compare with each other and with topical corticosteroids.  Some of these questions were answered in two recent studies.
  • Thom et al. compared individual data from two phase 3 studies of crisaborole ointment with previously published data for topical pimecrolimus and tacrolimus in patients ≥2 years with mild-to-moderate AD using an approach referred to as unanchored matching-adjusted indirect comparison. By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for crisaborole ointment vs. pimecrolimus cream and tacrolimus 0.03% ointment.
  • Salava et al. followed 152 children age 1-3 years with moderate-severe AD for 36 months. They found no significant differences of topical tacrolimus 0.03% or 0.1% ointment vs. low or mid potency topical corticosteroids on AD severity (as judged by the eczema area and severity index), skin or other infections, and various cytokine levels.

While these data do not replace the need for head-to-head studies, they do provide important context about comparative efficacy and safety of the various topical agents in our toolbox.

References

1. Ben Mordehai Y et al. Long-Term Narrowband UV-B Efficacy in Moderate to Severe Atopic Dermatitis. Dermatitis. 2021 (Nov 27).
2. Langer SS et al. Efficacy of house dust mite sublingual immunotherapy in patients with atopic dermatitis: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol Pract. 2021 (Nov 9).
3. Thom H et al. Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis Dermatol Ther (Heidelb). 2021 (Dec 8).
4. Salava A et al. Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis - a 36-month follow-up study. Clin Exp Dermatol. 2021 (Nov 19).

A new era of evidence-based practice for atopic dermatitis

Atopic dermatitis (AD) is one of the most common diseases of childhood and still very common in adults worldwide. AD is also a very burdensome disease with considerable patient-burden. Despite the enormous population- and patient- burden, there remain many unmet needs in the management of AD. In addition, many treatments commonly used in AD had scant or mixed evidence regarding their efficacy and safety. For example, topical corticosteroids (TCS) are the workhorse for treatment in AD and most other inflammatory skin diseases. Yet, virtually everything we know about the efficacy of TCS comes from vasoconstriction proxy assays with almost no studies formally studying the efficacy of TCS in AD. Similarly, many therapies used off-label to treat more severe AD, such as phototherapy or allergen immunotherapy have inconsistent evidence to guide their use. Well, things are finally changing and the evidence is coming in at a frenzied pace. Development of multiple novel therapeutics in AD led to renewed interest in studying the efficacy and safety of older therapies as well.

• Phototherapy is an important treatment modality in AD patients who have an inadequate response to topical therapy. Many different modalities and devices were used to treat AD over the years, including narrowband ultraviolet B (NBUVB) and ultraviolet A (UVA)-1. NBUVB is the most commonly used approach in the United States and some other regions of the world. Ben Mordehai et al. published the results of a retrospective cohort study of 390 Israeli patients with moderate-severe AD treated with NBUVB therapy between 2000-2017 with ≥3 years of follow-up. Overall, 55.4% achieved an Investigator’s Global Assessment score of clear or almost clear. Facial involvement, occurrence of adverse effects, fewer treatments, and pretreatment immunoglobulin E levels >4000 IU/ml were associated with poorer clinical response to NBUVB. Median duration of response was 12 months with more relapses in children (<18 years).

• House dust mites (HDM) were previously shown to be triggers of AD via Immunoglobulin E dependent and independent mechanisms. Unfortunately, HDM avoidance is challenging for patients and has not proven to be reliably effective in clinical trials. Previous studies examined different approaches for immunotherapy to HDM with mixed results. Langer et al. published the results of a randomized, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT) or placebo for 18 months in 91 children and adults with AD and positive skin test result and/or Immunoglobulin E to Dermatophagoides pteronyssinus. After 18 months, patients treated with HDM SLIT achieved greater reductions in the SCOring AD (SCORAD) index and were more likely to achieve an Investigator’s Global Assessment score of clear or almost clear compared to placebo. Headache and abdominal pain were the most common adverse events reported by both groups. Efficacy of HDM SLIT in this study was relatively modest. Nevertheless, it appears to be a safe therapy and a reasonable adjunctive therapy in patients with AD whose disease is believed to be triggered by HDM.

• We are fortunate to have multiple non-steroidal topical therapies for atopic dermatitis, including crisaborole ointment, pimecrolimus cream and tacrolimus ointment. A number of questions remain about how these therapies compare with each other and with topical corticosteroids.  Some of these questions were answered in two recent studies.
  • Thom et al. compared individual data from two phase 3 studies of crisaborole ointment with previously published data for topical pimecrolimus and tacrolimus in patients ≥2 years with mild-to-moderate AD using an approach referred to as unanchored matching-adjusted indirect comparison. By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for crisaborole ointment vs. pimecrolimus cream and tacrolimus 0.03% ointment.
  • Salava et al. followed 152 children age 1-3 years with moderate-severe AD for 36 months. They found no significant differences of topical tacrolimus 0.03% or 0.1% ointment vs. low or mid potency topical corticosteroids on AD severity (as judged by the eczema area and severity index), skin or other infections, and various cytokine levels.

While these data do not replace the need for head-to-head studies, they do provide important context about comparative efficacy and safety of the various topical agents in our toolbox.

References

1. Ben Mordehai Y et al. Long-Term Narrowband UV-B Efficacy in Moderate to Severe Atopic Dermatitis. Dermatitis. 2021 (Nov 27).
2. Langer SS et al. Efficacy of house dust mite sublingual immunotherapy in patients with atopic dermatitis: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol Pract. 2021 (Nov 9).
3. Thom H et al. Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis Dermatol Ther (Heidelb). 2021 (Dec 8).
4. Salava A et al. Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis - a 36-month follow-up study. Clin Exp Dermatol. 2021 (Nov 19).

A new era of evidence-based practice for atopic dermatitis

Atopic dermatitis (AD) is one of the most common diseases of childhood and still very common in adults worldwide. AD is also a very burdensome disease with considerable patient-burden. Despite the enormous population- and patient- burden, there remain many unmet needs in the management of AD. In addition, many treatments commonly used in AD had scant or mixed evidence regarding their efficacy and safety. For example, topical corticosteroids (TCS) are the workhorse for treatment in AD and most other inflammatory skin diseases. Yet, virtually everything we know about the efficacy of TCS comes from vasoconstriction proxy assays with almost no studies formally studying the efficacy of TCS in AD. Similarly, many therapies used off-label to treat more severe AD, such as phototherapy or allergen immunotherapy have inconsistent evidence to guide their use. Well, things are finally changing and the evidence is coming in at a frenzied pace. Development of multiple novel therapeutics in AD led to renewed interest in studying the efficacy and safety of older therapies as well.

• Phototherapy is an important treatment modality in AD patients who have an inadequate response to topical therapy. Many different modalities and devices were used to treat AD over the years, including narrowband ultraviolet B (NBUVB) and ultraviolet A (UVA)-1. NBUVB is the most commonly used approach in the United States and some other regions of the world. Ben Mordehai et al. published the results of a retrospective cohort study of 390 Israeli patients with moderate-severe AD treated with NBUVB therapy between 2000-2017 with ≥3 years of follow-up. Overall, 55.4% achieved an Investigator’s Global Assessment score of clear or almost clear. Facial involvement, occurrence of adverse effects, fewer treatments, and pretreatment immunoglobulin E levels >4000 IU/ml were associated with poorer clinical response to NBUVB. Median duration of response was 12 months with more relapses in children (<18 years).

• House dust mites (HDM) were previously shown to be triggers of AD via Immunoglobulin E dependent and independent mechanisms. Unfortunately, HDM avoidance is challenging for patients and has not proven to be reliably effective in clinical trials. Previous studies examined different approaches for immunotherapy to HDM with mixed results. Langer et al. published the results of a randomized, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT) or placebo for 18 months in 91 children and adults with AD and positive skin test result and/or Immunoglobulin E to Dermatophagoides pteronyssinus. After 18 months, patients treated with HDM SLIT achieved greater reductions in the SCOring AD (SCORAD) index and were more likely to achieve an Investigator’s Global Assessment score of clear or almost clear compared to placebo. Headache and abdominal pain were the most common adverse events reported by both groups. Efficacy of HDM SLIT in this study was relatively modest. Nevertheless, it appears to be a safe therapy and a reasonable adjunctive therapy in patients with AD whose disease is believed to be triggered by HDM.

• We are fortunate to have multiple non-steroidal topical therapies for atopic dermatitis, including crisaborole ointment, pimecrolimus cream and tacrolimus ointment. A number of questions remain about how these therapies compare with each other and with topical corticosteroids.  Some of these questions were answered in two recent studies.
  • Thom et al. compared individual data from two phase 3 studies of crisaborole ointment with previously published data for topical pimecrolimus and tacrolimus in patients ≥2 years with mild-to-moderate AD using an approach referred to as unanchored matching-adjusted indirect comparison. By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for crisaborole ointment vs. pimecrolimus cream and tacrolimus 0.03% ointment.
  • Salava et al. followed 152 children age 1-3 years with moderate-severe AD for 36 months. They found no significant differences of topical tacrolimus 0.03% or 0.1% ointment vs. low or mid potency topical corticosteroids on AD severity (as judged by the eczema area and severity index), skin or other infections, and various cytokine levels.

While these data do not replace the need for head-to-head studies, they do provide important context about comparative efficacy and safety of the various topical agents in our toolbox.

References

1. Ben Mordehai Y et al. Long-Term Narrowband UV-B Efficacy in Moderate to Severe Atopic Dermatitis. Dermatitis. 2021 (Nov 27).
2. Langer SS et al. Efficacy of house dust mite sublingual immunotherapy in patients with atopic dermatitis: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol Pract. 2021 (Nov 9).
3. Thom H et al. Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis Dermatol Ther (Heidelb). 2021 (Dec 8).
4. Salava A et al. Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis - a 36-month follow-up study. Clin Exp Dermatol. 2021 (Nov 19).

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Atopic dermatitis (AD) is a complex disease with varying degrees of itch, pain, eczematous skin lesions and quality of life impact. Research over the past decade uncovered myriad associations of AD with comorbid health disorders. There are well-established associations of AD with atopic comorbidities in children and adults, including asthma, hay fever, food allergies and less commonly eosinophilic esophagitis. AD is also associated with higher rates of mental health disorders, including depression, anxiety and attention deficit (hyperactivity) disorder.

AD patients also have multiple risk factors for hypertension, including chronic sleep deprivation and limitations on physical activity from itch. Yousaf et al conducted a systematic literature review and meta-analysis of 19 studies and found significantly increased likelihood of hypertension in patients with AD compared to healthy controls, particularly moderate-to-severe AD. Though, the odds of hypertension were lower in patients with AD compared to psoriasis.

Sleep disturbances (SD) are also common in AD patients. Manjunath et al conducted a cross-sectional, dermatology practice-based study to examine clinical differences in geriatric vs younger adult AD patients. Geriatric age was not associated with any significant differences of AD severity. However, geriatric AD patients had significantly more nights of SD, particularly trouble staying asleep, and increased fatigue than younger adults. In general, having good sleep hygiene and getting adequate sleep are important for overall health and longevity. SD therefore warrant particular attention in clinical management of AD as they are often modifiable with improved AD control.

Likewise, the myriad comorbidities associated with AD may lead to poorer health outcomes, such as hospitalization. Edigin et al conducted a longitudinal study of 23,410 adults hospitalized in the United States with AD. Hospitalizations rates increased between 1998 and 2018 owing to comorbid health disorders, but not AD itself.

Together, these results highlight the importance of holistic management of AD patients, including atopic and non-atopic comorbidities. However, many questions remain about how and when to best screen for various comorbidities. Generally, more severe AD is one of the strongest predictors of atopic and mental health comorbidities, as well as sleep disturbances and hypertension as shown in the abovementioned studies. Additionally, geriatric AD patients warrant closer monitoring of SD. Of course, screening patients for these comorbidities can take up precious time in a busy clinical practice. Though, it is a worthwhile investment of time and will improve patients’ health outcomes and the quality of care you provide for patients.

Atopic dermatitis (AD) is a complex disease with varying degrees of itch, pain, eczematous skin lesions and quality of life impact. Research over the past decade uncovered myriad associations of AD with comorbid health disorders. There are well-established associations of AD with atopic comorbidities in children and adults, including asthma, hay fever, food allergies and less commonly eosinophilic esophagitis. AD is also associated with higher rates of mental health disorders, including depression, anxiety and attention deficit (hyperactivity) disorder.

AD patients also have multiple risk factors for hypertension, including chronic sleep deprivation and limitations on physical activity from itch. Yousaf et al conducted a systematic literature review and meta-analysis of 19 studies and found significantly increased likelihood of hypertension in patients with AD compared to healthy controls, particularly moderate-to-severe AD. Though, the odds of hypertension were lower in patients with AD compared to psoriasis.

Sleep disturbances (SD) are also common in AD patients. Manjunath et al conducted a cross-sectional, dermatology practice-based study to examine clinical differences in geriatric vs younger adult AD patients. Geriatric age was not associated with any significant differences of AD severity. However, geriatric AD patients had significantly more nights of SD, particularly trouble staying asleep, and increased fatigue than younger adults. In general, having good sleep hygiene and getting adequate sleep are important for overall health and longevity. SD therefore warrant particular attention in clinical management of AD as they are often modifiable with improved AD control.

Likewise, the myriad comorbidities associated with AD may lead to poorer health outcomes, such as hospitalization. Edigin et al conducted a longitudinal study of 23,410 adults hospitalized in the United States with AD. Hospitalizations rates increased between 1998 and 2018 owing to comorbid health disorders, but not AD itself.

Together, these results highlight the importance of holistic management of AD patients, including atopic and non-atopic comorbidities. However, many questions remain about how and when to best screen for various comorbidities. Generally, more severe AD is one of the strongest predictors of atopic and mental health comorbidities, as well as sleep disturbances and hypertension as shown in the abovementioned studies. Additionally, geriatric AD patients warrant closer monitoring of SD. Of course, screening patients for these comorbidities can take up precious time in a busy clinical practice. Though, it is a worthwhile investment of time and will improve patients’ health outcomes and the quality of care you provide for patients.

Atopic dermatitis (AD) is a complex disease with varying degrees of itch, pain, eczematous skin lesions and quality of life impact. Research over the past decade uncovered myriad associations of AD with comorbid health disorders. There are well-established associations of AD with atopic comorbidities in children and adults, including asthma, hay fever, food allergies and less commonly eosinophilic esophagitis. AD is also associated with higher rates of mental health disorders, including depression, anxiety and attention deficit (hyperactivity) disorder.

AD patients also have multiple risk factors for hypertension, including chronic sleep deprivation and limitations on physical activity from itch. Yousaf et al conducted a systematic literature review and meta-analysis of 19 studies and found significantly increased likelihood of hypertension in patients with AD compared to healthy controls, particularly moderate-to-severe AD. Though, the odds of hypertension were lower in patients with AD compared to psoriasis.

Sleep disturbances (SD) are also common in AD patients. Manjunath et al conducted a cross-sectional, dermatology practice-based study to examine clinical differences in geriatric vs younger adult AD patients. Geriatric age was not associated with any significant differences of AD severity. However, geriatric AD patients had significantly more nights of SD, particularly trouble staying asleep, and increased fatigue than younger adults. In general, having good sleep hygiene and getting adequate sleep are important for overall health and longevity. SD therefore warrant particular attention in clinical management of AD as they are often modifiable with improved AD control.

Likewise, the myriad comorbidities associated with AD may lead to poorer health outcomes, such as hospitalization. Edigin et al conducted a longitudinal study of 23,410 adults hospitalized in the United States with AD. Hospitalizations rates increased between 1998 and 2018 owing to comorbid health disorders, but not AD itself.

Together, these results highlight the importance of holistic management of AD patients, including atopic and non-atopic comorbidities. However, many questions remain about how and when to best screen for various comorbidities. Generally, more severe AD is one of the strongest predictors of atopic and mental health comorbidities, as well as sleep disturbances and hypertension as shown in the abovementioned studies. Additionally, geriatric AD patients warrant closer monitoring of SD. Of course, screening patients for these comorbidities can take up precious time in a busy clinical practice. Though, it is a worthwhile investment of time and will improve patients’ health outcomes and the quality of care you provide for patients.

Atopic Dermatitis (AD) is complex with heterogeneous symptoms (e.g. skin-pain, sleep disturbance), signs (e.g. lichenification, prurigo nodules, follicular accentuation), and longitudinal course (intermittent, persistent). These disparate signs and symptoms should be addressed in optimize disease control.

Multiple extracellular cytokines are upregulated in skin of AD patients, including interleukins 4, 5, 13, 22, 31 and thymic stromal lymphopoietin, all of which signal intracellularly through Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathways. Differential cytokine expression is proposed to underlie clinical variability. It may be necessary to inhibit signaling of multiple cytokines to achieve adequate control of AD.

Dupilumab is currently the only biologic treatment approved in the United States for moderate-severe AD. Dupilumab revolutionized AD management. However, there remain unmet needs, including the need for faster and more potent efficacy, and oral treatment options. Recently, oral JAK-inhibitors were investigated as treatments for moderate-severe AD. Multiple JAK-inhibitors demonstrated strong and rapid efficacy across multiple clinician-reported and patient-reported outcomes.

• Miao et al. recently conducted a meta-analysis of 10 randomized controlled trials and found that patients receiving JAK inhibitors showed significantly higher efficacy for eczema area and severity index (EASI) and Numeric Rating Scale (NRS)-itch scores and similar rates of adverse-events.
• Kim et al. pooled data from 3 randomized controlled trials of abrocitinib and found significantly higher proportions of clinically meaningful responses for itch in patients receiving abrocitinib 200 mg and 100 mg vs placebo as early as week 2 which continued through week 12.
• Lio et al. performed a post-hoc analysis of a phase 3 study of conducted in North America and found significant improvements for itch severity and sleep disturbance in patients treated with baricitinib 1 mg and 2 mg vs placebo. In particular, patients who achieved improvement of itch or sleep disturbance compared to those who did not were more likely to report having no impact on quality of life impact and improved work productivity.

This new therapeutic class will be an important addition to our therapeutic armamentarium and has potential to transform the AD treatment landscape.

• Many patients prefer taking pills over injections.
• Rapid-onset of efficacy for JAK-inhibitors will certainly be appreciated by patients, especially when trying to control tough flares. It may even guide clinical decision-making. Patients who have a good clinical response to JAK-inhibitors tend to do so within 4-8 weeks. By 8 weeks, if patients have no clinical response, they are likely not going to respond and may benefit from switching to alternative therapies.
• JAK-inhibitors can have robust efficacy, with higher doses of upadacitinib and abrocritinib showing greater efficacy than dupilumab at 12-16 weeks. This makes them attractive options to consider in patients who previously failed dupilumab.
• On the other hand, JAK-inhibitors have laboratory monitoring requirements, including complete blood count, comprehensive metabolic panel, lipid panel, etc.
• JAK-inhibitors warrant adverse-event monitoring for headache, nausea, acne, herpesvirus infections, risk of venous thromboembolism, etc.

Future research is needed to identify patient subsets who will benefit most from JAK-inhibitor therapy and where to position these agents in treatment guidelines.

Atopic Dermatitis (AD) is complex with heterogeneous symptoms (e.g. skin-pain, sleep disturbance), signs (e.g. lichenification, prurigo nodules, follicular accentuation), and longitudinal course (intermittent, persistent). These disparate signs and symptoms should be addressed in optimize disease control.

Multiple extracellular cytokines are upregulated in skin of AD patients, including interleukins 4, 5, 13, 22, 31 and thymic stromal lymphopoietin, all of which signal intracellularly through Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathways. Differential cytokine expression is proposed to underlie clinical variability. It may be necessary to inhibit signaling of multiple cytokines to achieve adequate control of AD.

Dupilumab is currently the only biologic treatment approved in the United States for moderate-severe AD. Dupilumab revolutionized AD management. However, there remain unmet needs, including the need for faster and more potent efficacy, and oral treatment options. Recently, oral JAK-inhibitors were investigated as treatments for moderate-severe AD. Multiple JAK-inhibitors demonstrated strong and rapid efficacy across multiple clinician-reported and patient-reported outcomes.

• Miao et al. recently conducted a meta-analysis of 10 randomized controlled trials and found that patients receiving JAK inhibitors showed significantly higher efficacy for eczema area and severity index (EASI) and Numeric Rating Scale (NRS)-itch scores and similar rates of adverse-events.
• Kim et al. pooled data from 3 randomized controlled trials of abrocitinib and found significantly higher proportions of clinically meaningful responses for itch in patients receiving abrocitinib 200 mg and 100 mg vs placebo as early as week 2 which continued through week 12.
• Lio et al. performed a post-hoc analysis of a phase 3 study of conducted in North America and found significant improvements for itch severity and sleep disturbance in patients treated with baricitinib 1 mg and 2 mg vs placebo. In particular, patients who achieved improvement of itch or sleep disturbance compared to those who did not were more likely to report having no impact on quality of life impact and improved work productivity.

This new therapeutic class will be an important addition to our therapeutic armamentarium and has potential to transform the AD treatment landscape.

• Many patients prefer taking pills over injections.
• Rapid-onset of efficacy for JAK-inhibitors will certainly be appreciated by patients, especially when trying to control tough flares. It may even guide clinical decision-making. Patients who have a good clinical response to JAK-inhibitors tend to do so within 4-8 weeks. By 8 weeks, if patients have no clinical response, they are likely not going to respond and may benefit from switching to alternative therapies.
• JAK-inhibitors can have robust efficacy, with higher doses of upadacitinib and abrocritinib showing greater efficacy than dupilumab at 12-16 weeks. This makes them attractive options to consider in patients who previously failed dupilumab.
• On the other hand, JAK-inhibitors have laboratory monitoring requirements, including complete blood count, comprehensive metabolic panel, lipid panel, etc.
• JAK-inhibitors warrant adverse-event monitoring for headache, nausea, acne, herpesvirus infections, risk of venous thromboembolism, etc.

Future research is needed to identify patient subsets who will benefit most from JAK-inhibitor therapy and where to position these agents in treatment guidelines.

Atopic Dermatitis (AD) is complex with heterogeneous symptoms (e.g. skin-pain, sleep disturbance), signs (e.g. lichenification, prurigo nodules, follicular accentuation), and longitudinal course (intermittent, persistent). These disparate signs and symptoms should be addressed in optimize disease control.

Multiple extracellular cytokines are upregulated in skin of AD patients, including interleukins 4, 5, 13, 22, 31 and thymic stromal lymphopoietin, all of which signal intracellularly through Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathways. Differential cytokine expression is proposed to underlie clinical variability. It may be necessary to inhibit signaling of multiple cytokines to achieve adequate control of AD.

Dupilumab is currently the only biologic treatment approved in the United States for moderate-severe AD. Dupilumab revolutionized AD management. However, there remain unmet needs, including the need for faster and more potent efficacy, and oral treatment options. Recently, oral JAK-inhibitors were investigated as treatments for moderate-severe AD. Multiple JAK-inhibitors demonstrated strong and rapid efficacy across multiple clinician-reported and patient-reported outcomes.

• Miao et al. recently conducted a meta-analysis of 10 randomized controlled trials and found that patients receiving JAK inhibitors showed significantly higher efficacy for eczema area and severity index (EASI) and Numeric Rating Scale (NRS)-itch scores and similar rates of adverse-events.
• Kim et al. pooled data from 3 randomized controlled trials of abrocitinib and found significantly higher proportions of clinically meaningful responses for itch in patients receiving abrocitinib 200 mg and 100 mg vs placebo as early as week 2 which continued through week 12.
• Lio et al. performed a post-hoc analysis of a phase 3 study of conducted in North America and found significant improvements for itch severity and sleep disturbance in patients treated with baricitinib 1 mg and 2 mg vs placebo. In particular, patients who achieved improvement of itch or sleep disturbance compared to those who did not were more likely to report having no impact on quality of life impact and improved work productivity.

This new therapeutic class will be an important addition to our therapeutic armamentarium and has potential to transform the AD treatment landscape.

• Many patients prefer taking pills over injections.
• Rapid-onset of efficacy for JAK-inhibitors will certainly be appreciated by patients, especially when trying to control tough flares. It may even guide clinical decision-making. Patients who have a good clinical response to JAK-inhibitors tend to do so within 4-8 weeks. By 8 weeks, if patients have no clinical response, they are likely not going to respond and may benefit from switching to alternative therapies.
• JAK-inhibitors can have robust efficacy, with higher doses of upadacitinib and abrocritinib showing greater efficacy than dupilumab at 12-16 weeks. This makes them attractive options to consider in patients who previously failed dupilumab.
• On the other hand, JAK-inhibitors have laboratory monitoring requirements, including complete blood count, comprehensive metabolic panel, lipid panel, etc.
• JAK-inhibitors warrant adverse-event monitoring for headache, nausea, acne, herpesvirus infections, risk of venous thromboembolism, etc.

Future research is needed to identify patient subsets who will benefit most from JAK-inhibitor therapy and where to position these agents in treatment guidelines.