User login
Commentary: Prevention in AD, December 2022
We are in the golden age of atopic dermatitis (AD) drug development. We are fortunate to have numerous topicals, oral systemics, and biologics recently approved or in late-stage clinical development. Yet, we are still lacking effective strategies for primary prevention of incident AD and secondary prevention of AD exacerbations.
Kottner and colleagues published the results from the ADAPI study of 150 infants who were at an enhanced risk for AD. The children were randomly assigned to receive either a skincare regimen that was standardized or unstandardized skincare preferred by parents. They found that in the first year of life, the overall cumulative incidence rate of AD was similar between standardized skincare and skincare preferred by parents (P = .999).
Bradshaw and colleagues also published results from the BEEP study (a 5-year prospective study) of 1394 infants who were at high risk for AD. The children were randomly assigned to receive either emollient for the first year plus standard skincare or standard skincare alone. They found a similar proportion of children were clinically diagnosed with AD between 12 and 60 months in the emollient plus skincare group vs skincare alone group (31% vs 28%; adjusted relative risk 1.10; 95% CI 0.93-1.30). Unfortunately, the results from both studies are consistent with earlier results from BEEP, as well as other studies, and did not show that early application of emollients successfully prevent AD.
The use of applying emollients for primary prevention is unclear. However, proactive application of topical corticosteroids (TCS) and other topical nonsteroidal agents is well accepted in AD treatment guidelines for secondary prevention of AD exacerbations.1 Although, a recent study from Kamiya and colleagues suggested that proactive application of topical corticosteroids may not work as well as we think. They conducted an open-label, active-controlled, parallel-group study of 49 pediatric patients with moderate to severe AD who achieved remission with potent TCS. The children were then randomly assigned to receive proactive therapy with or discontinuation of TCS. The authors found no significant decrease in relapse rates with proactive vs no proactive treatment groups (8.33% vs 20.0%; P = .0859). I don't think these results will change our guidelines. But I do think these results raise important questions about the myriad aspects of proactive therapy that require appropriate counseling, including frequency of application per week (1-3 times), choice of therapies (corticosteroid or nonsteroidal agent), additional emollient use, bathing practice, etc. I personally would strongly recommend use of proactive therapy in clinical practice, but these results highlight that it is not a magic bullet for all patients either.
Additional Reference
- Boguniewicz M, Fonacier L, Guttman-Yassky E, et al. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120:10-22.e2. Doi: 10.1016/j.anai.2017.10.039
We are in the golden age of atopic dermatitis (AD) drug development. We are fortunate to have numerous topicals, oral systemics, and biologics recently approved or in late-stage clinical development. Yet, we are still lacking effective strategies for primary prevention of incident AD and secondary prevention of AD exacerbations.
Kottner and colleagues published the results from the ADAPI study of 150 infants who were at an enhanced risk for AD. The children were randomly assigned to receive either a skincare regimen that was standardized or unstandardized skincare preferred by parents. They found that in the first year of life, the overall cumulative incidence rate of AD was similar between standardized skincare and skincare preferred by parents (P = .999).
Bradshaw and colleagues also published results from the BEEP study (a 5-year prospective study) of 1394 infants who were at high risk for AD. The children were randomly assigned to receive either emollient for the first year plus standard skincare or standard skincare alone. They found a similar proportion of children were clinically diagnosed with AD between 12 and 60 months in the emollient plus skincare group vs skincare alone group (31% vs 28%; adjusted relative risk 1.10; 95% CI 0.93-1.30). Unfortunately, the results from both studies are consistent with earlier results from BEEP, as well as other studies, and did not show that early application of emollients successfully prevent AD.
The use of applying emollients for primary prevention is unclear. However, proactive application of topical corticosteroids (TCS) and other topical nonsteroidal agents is well accepted in AD treatment guidelines for secondary prevention of AD exacerbations.1 Although, a recent study from Kamiya and colleagues suggested that proactive application of topical corticosteroids may not work as well as we think. They conducted an open-label, active-controlled, parallel-group study of 49 pediatric patients with moderate to severe AD who achieved remission with potent TCS. The children were then randomly assigned to receive proactive therapy with or discontinuation of TCS. The authors found no significant decrease in relapse rates with proactive vs no proactive treatment groups (8.33% vs 20.0%; P = .0859). I don't think these results will change our guidelines. But I do think these results raise important questions about the myriad aspects of proactive therapy that require appropriate counseling, including frequency of application per week (1-3 times), choice of therapies (corticosteroid or nonsteroidal agent), additional emollient use, bathing practice, etc. I personally would strongly recommend use of proactive therapy in clinical practice, but these results highlight that it is not a magic bullet for all patients either.
Additional Reference
- Boguniewicz M, Fonacier L, Guttman-Yassky E, et al. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120:10-22.e2. Doi: 10.1016/j.anai.2017.10.039
We are in the golden age of atopic dermatitis (AD) drug development. We are fortunate to have numerous topicals, oral systemics, and biologics recently approved or in late-stage clinical development. Yet, we are still lacking effective strategies for primary prevention of incident AD and secondary prevention of AD exacerbations.
Kottner and colleagues published the results from the ADAPI study of 150 infants who were at an enhanced risk for AD. The children were randomly assigned to receive either a skincare regimen that was standardized or unstandardized skincare preferred by parents. They found that in the first year of life, the overall cumulative incidence rate of AD was similar between standardized skincare and skincare preferred by parents (P = .999).
Bradshaw and colleagues also published results from the BEEP study (a 5-year prospective study) of 1394 infants who were at high risk for AD. The children were randomly assigned to receive either emollient for the first year plus standard skincare or standard skincare alone. They found a similar proportion of children were clinically diagnosed with AD between 12 and 60 months in the emollient plus skincare group vs skincare alone group (31% vs 28%; adjusted relative risk 1.10; 95% CI 0.93-1.30). Unfortunately, the results from both studies are consistent with earlier results from BEEP, as well as other studies, and did not show that early application of emollients successfully prevent AD.
The use of applying emollients for primary prevention is unclear. However, proactive application of topical corticosteroids (TCS) and other topical nonsteroidal agents is well accepted in AD treatment guidelines for secondary prevention of AD exacerbations.1 Although, a recent study from Kamiya and colleagues suggested that proactive application of topical corticosteroids may not work as well as we think. They conducted an open-label, active-controlled, parallel-group study of 49 pediatric patients with moderate to severe AD who achieved remission with potent TCS. The children were then randomly assigned to receive proactive therapy with or discontinuation of TCS. The authors found no significant decrease in relapse rates with proactive vs no proactive treatment groups (8.33% vs 20.0%; P = .0859). I don't think these results will change our guidelines. But I do think these results raise important questions about the myriad aspects of proactive therapy that require appropriate counseling, including frequency of application per week (1-3 times), choice of therapies (corticosteroid or nonsteroidal agent), additional emollient use, bathing practice, etc. I personally would strongly recommend use of proactive therapy in clinical practice, but these results highlight that it is not a magic bullet for all patients either.
Additional Reference
- Boguniewicz M, Fonacier L, Guttman-Yassky E, et al. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120:10-22.e2. Doi: 10.1016/j.anai.2017.10.039
Commentary: Complementary treatments for AD, November 2022
Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.
Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.
Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.
For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.
Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.
Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.
Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.
For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.
Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.
Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.
Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.
For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.
Commentary: New Topical Approaches Hit the Spots (and the Itch) for AD, October 2022
The Janus kinase (JAK) family has become a popular target for novel drug development. There are four JAK subunits, JAK1, JAK2, JAK3, and TYK2, each playing different roles in vital immunologic, hematologic, and homeostatic functions. A wide array of topical JAK-inhibitors has been or are currently being investigated for the treatment of AD, each with different profiles of selectivity across the JAK family.
Ruxolitinib is a preferential JAK1 and JAK2 inhibitor. Oral ruxolitinib is currently approved for the treatment of myelofibrosis. Topical ruxolitinib cream is also approved in the United States for the treatment of mild-to-moderate AD and, more recently, vitiligo.
Blauvelt and colleagues published the findings from a post hoc analysis of data related to itch responses from two randomized, double-blind, vehicle-controlled, phase 3 studies of patients with mild-to-moderate AD. Topical ruxolitinib applied twice daily led to a significant increase in the proportion of patients achieving at least a 2-point or 4-point reduction in Peak Pruritus Numeric Rating Scale (PP-NRS) within 12 hours of initial application and continued improvements out to week 8. Patients treated with ruxolitinib cream were also significantly more likely to achieve an itch-free state and faster reductions in itch compared with vehicle. Rapid improvement of itch is an important feature for any topical therapy that may be used as needed for AD flares.
Brepocitinib is a preferential JAK1 and tyrosine kinase 2 inhibitor. Oral brepocitinib is currently under investigation for several immune-mediated disorders, including dermatomyositis and lupus. Topical brepocitinib cream was also studied in a randomized, double-blind, vehicle-controlled, phase 2 study of patients with mild-to-moderate AD. Brepocitinib cream applied daily or twice daily led to significant decreases in the Eczema Area and Severity Index (EASI), increases in the proportion of patients who achieved Investigator Global Assessment (IGA) scores of clear or almost clear, EASI-75 responses, and 2-point or 4-point reductions in PP-NRS. Overall, topical brepocitinib was well tolerated. Though more studies are needed, topical brepocitinib may become an important addition to our toolbox for managing AD and perhaps other chronic inflammatory skin diseases.
Let's move along to yet another novel mechanism studied in AD: ectoine. Ectoine is a naturally derived chemical from some bacteria that can act as an osmolyte and protect organisms from osmotic stress. It is used in some skin care products because it can protect against xerosis and ultraviolet exposure. Alexopoulos and colleagues published the results of a randomized, single-blind, vehicle-controlled study of a novel cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) in children with mild-to-moderate AD. At week 4, application of EHA cream led to significant decreases in SCORing AD (SCORAD) and IGA scores compared with vehicle cream as well all secondary outcome measures. EHA cream was well-tolerated overall, with most adverse events being cutaneous and mild.
All of these topical agents were studied as "reactive" therapies, ie, to be applied to active AD lesions. It would be nice to have approaches that can also prevent AD. Ní Chaoimh and colleagues published findings from the STOP AD trial that examined whether routine application of emollients in the first 8 weeks of life can prevent AD at age 12 months. They found that early emollient use resulted in significantly lower incidence of AD and similar rates of skin infections at age 12 months. Previous studies found mixed results regarding the efficacy of routine application of emollients in newborns. Though more studies are needed, these results are promising and suggest that early life use of emollients could be a cheap, feasible, and effective option to prevent AD.
The Janus kinase (JAK) family has become a popular target for novel drug development. There are four JAK subunits, JAK1, JAK2, JAK3, and TYK2, each playing different roles in vital immunologic, hematologic, and homeostatic functions. A wide array of topical JAK-inhibitors has been or are currently being investigated for the treatment of AD, each with different profiles of selectivity across the JAK family.
Ruxolitinib is a preferential JAK1 and JAK2 inhibitor. Oral ruxolitinib is currently approved for the treatment of myelofibrosis. Topical ruxolitinib cream is also approved in the United States for the treatment of mild-to-moderate AD and, more recently, vitiligo.
Blauvelt and colleagues published the findings from a post hoc analysis of data related to itch responses from two randomized, double-blind, vehicle-controlled, phase 3 studies of patients with mild-to-moderate AD. Topical ruxolitinib applied twice daily led to a significant increase in the proportion of patients achieving at least a 2-point or 4-point reduction in Peak Pruritus Numeric Rating Scale (PP-NRS) within 12 hours of initial application and continued improvements out to week 8. Patients treated with ruxolitinib cream were also significantly more likely to achieve an itch-free state and faster reductions in itch compared with vehicle. Rapid improvement of itch is an important feature for any topical therapy that may be used as needed for AD flares.
Brepocitinib is a preferential JAK1 and tyrosine kinase 2 inhibitor. Oral brepocitinib is currently under investigation for several immune-mediated disorders, including dermatomyositis and lupus. Topical brepocitinib cream was also studied in a randomized, double-blind, vehicle-controlled, phase 2 study of patients with mild-to-moderate AD. Brepocitinib cream applied daily or twice daily led to significant decreases in the Eczema Area and Severity Index (EASI), increases in the proportion of patients who achieved Investigator Global Assessment (IGA) scores of clear or almost clear, EASI-75 responses, and 2-point or 4-point reductions in PP-NRS. Overall, topical brepocitinib was well tolerated. Though more studies are needed, topical brepocitinib may become an important addition to our toolbox for managing AD and perhaps other chronic inflammatory skin diseases.
Let's move along to yet another novel mechanism studied in AD: ectoine. Ectoine is a naturally derived chemical from some bacteria that can act as an osmolyte and protect organisms from osmotic stress. It is used in some skin care products because it can protect against xerosis and ultraviolet exposure. Alexopoulos and colleagues published the results of a randomized, single-blind, vehicle-controlled study of a novel cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) in children with mild-to-moderate AD. At week 4, application of EHA cream led to significant decreases in SCORing AD (SCORAD) and IGA scores compared with vehicle cream as well all secondary outcome measures. EHA cream was well-tolerated overall, with most adverse events being cutaneous and mild.
All of these topical agents were studied as "reactive" therapies, ie, to be applied to active AD lesions. It would be nice to have approaches that can also prevent AD. Ní Chaoimh and colleagues published findings from the STOP AD trial that examined whether routine application of emollients in the first 8 weeks of life can prevent AD at age 12 months. They found that early emollient use resulted in significantly lower incidence of AD and similar rates of skin infections at age 12 months. Previous studies found mixed results regarding the efficacy of routine application of emollients in newborns. Though more studies are needed, these results are promising and suggest that early life use of emollients could be a cheap, feasible, and effective option to prevent AD.
The Janus kinase (JAK) family has become a popular target for novel drug development. There are four JAK subunits, JAK1, JAK2, JAK3, and TYK2, each playing different roles in vital immunologic, hematologic, and homeostatic functions. A wide array of topical JAK-inhibitors has been or are currently being investigated for the treatment of AD, each with different profiles of selectivity across the JAK family.
Ruxolitinib is a preferential JAK1 and JAK2 inhibitor. Oral ruxolitinib is currently approved for the treatment of myelofibrosis. Topical ruxolitinib cream is also approved in the United States for the treatment of mild-to-moderate AD and, more recently, vitiligo.
Blauvelt and colleagues published the findings from a post hoc analysis of data related to itch responses from two randomized, double-blind, vehicle-controlled, phase 3 studies of patients with mild-to-moderate AD. Topical ruxolitinib applied twice daily led to a significant increase in the proportion of patients achieving at least a 2-point or 4-point reduction in Peak Pruritus Numeric Rating Scale (PP-NRS) within 12 hours of initial application and continued improvements out to week 8. Patients treated with ruxolitinib cream were also significantly more likely to achieve an itch-free state and faster reductions in itch compared with vehicle. Rapid improvement of itch is an important feature for any topical therapy that may be used as needed for AD flares.
Brepocitinib is a preferential JAK1 and tyrosine kinase 2 inhibitor. Oral brepocitinib is currently under investigation for several immune-mediated disorders, including dermatomyositis and lupus. Topical brepocitinib cream was also studied in a randomized, double-blind, vehicle-controlled, phase 2 study of patients with mild-to-moderate AD. Brepocitinib cream applied daily or twice daily led to significant decreases in the Eczema Area and Severity Index (EASI), increases in the proportion of patients who achieved Investigator Global Assessment (IGA) scores of clear or almost clear, EASI-75 responses, and 2-point or 4-point reductions in PP-NRS. Overall, topical brepocitinib was well tolerated. Though more studies are needed, topical brepocitinib may become an important addition to our toolbox for managing AD and perhaps other chronic inflammatory skin diseases.
Let's move along to yet another novel mechanism studied in AD: ectoine. Ectoine is a naturally derived chemical from some bacteria that can act as an osmolyte and protect organisms from osmotic stress. It is used in some skin care products because it can protect against xerosis and ultraviolet exposure. Alexopoulos and colleagues published the results of a randomized, single-blind, vehicle-controlled study of a novel cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) in children with mild-to-moderate AD. At week 4, application of EHA cream led to significant decreases in SCORing AD (SCORAD) and IGA scores compared with vehicle cream as well all secondary outcome measures. EHA cream was well-tolerated overall, with most adverse events being cutaneous and mild.
All of these topical agents were studied as "reactive" therapies, ie, to be applied to active AD lesions. It would be nice to have approaches that can also prevent AD. Ní Chaoimh and colleagues published findings from the STOP AD trial that examined whether routine application of emollients in the first 8 weeks of life can prevent AD at age 12 months. They found that early emollient use resulted in significantly lower incidence of AD and similar rates of skin infections at age 12 months. Previous studies found mixed results regarding the efficacy of routine application of emollients in newborns. Though more studies are needed, these results are promising and suggest that early life use of emollients could be a cheap, feasible, and effective option to prevent AD.
Commentary: Something for Everyone in AD Treatment, September 2022
Let's start with tralokinumab. I previously had the privilege of being lead author on a study of the efficacy of tralokinumab beyond week 16 — the ECZTRA3 study.1 ECZTRA3 studied tralokinumab at the approved dose (600 mg loading dose followed by 300 mg every other week) vs placebo with concomitant topical corticosteroids (TCS) for an initial 16-week treatment period. Patients who achieved an Investigator's Global Assessment (IGA) score of 0 or 1 or 75% improvement in the Eczema Area and Severity Index (EASI-75) response were then randomly assigned again to receive 300 mg tralokinumab either continuously at every-other-week intervals or a prolonged interval of every 4 weeks (again with concomitant TCS).
With ECZTRA3, we found that patients continued to improve on tralokinumab + TCS well beyond week 16, with increased EASI-75 responses (week 16: 56%; week 32: 70.2%) and sustained or increased improvement across multiple patient-reported outcomes. Together, these results indicate that clinical responses may take more than 16 weeks to achieve with tralokinumab. In addition, some patients may be able to maintain clinical responses using fewer injections at 4-week intervals. This may allow tailoring dosing to individual patient needs. In fact, tralokinumab is approved in the United States and other regions with the option of every-2-week or every-4-week maintenance dosing in patients who have a good clinical response at week 16.
Since AD can be a lifelong disease, we expect that some patients will need to remain on various therapies for extended periods of time, perhaps many years, in order to maintain long-term control. It is imperative that any long-term treatment demonstrate a good long-term safety and efficacy profile. Blauvelt and colleagues published 2-year interim results from the ongoing ECZTEND long-term, open-label extension study of tralokinumab. They showed no new safety signals and stable rates of adverse events compared with earlier time points. Additionally, they showed that 82.5% of patients treated with open-label tralokinumab + TCS for 2 years maintained EASI-75 responses. These data are reassuring and support the potential use of tralokinumab as a long-term treatment option in AD.
While dupilumab is not approved for every-4-week maintenance dosing, a recent study by Spekhorst and colleagues confirmed that dupilumab can also be safely and effectively administered at intervals of every 4 weeks or every 6-8 weeks. Analyzing data from the BioDay real-world observational registry, they found that among patients who achieved good clinical responses (EASI scores ≤ 7) after 52 weeks of treatment with dupilumab administered every 2 weeks, many patients were able to maintain those responses at 3 months after the interval of administration was increased to every 4 weeks (> 80%) or 6-8 weeks (93.3%). These real-world data confirm the results previously observed in the phase 3 SOLO-CONTINUE study2 and support the use of maintenance dosing of dupilumab at prolonged intervals, though such use would technically be considered off-label.
Let’s also review some new data for abrocitinib, a once-daily oral preferential Janus kinase (JAK) 1 inhibitor. Reich and colleagues reported results from a phase 3 trial of adults with moderate-to-severe AD that compared the safety and efficacy of oral abrocitinib at the higher 200 mg dose vs subcutaneous dupilumab over 26 weeks. They found that more patients achieved ≥ 4-point improvement in the Peak Pruritus Numerical Rating Scale score at week 2 with 200 mg abrocitinib compared with 300 mg dupilumab every other week (48% vs 26%). There were also improved EASI-90 responses at week 4 (29% vs 15%). A dose of 200 mg abrocitinib was also significantly more effective than dupilumab for a number of additional investigator- and patient-reported outcomes. In general, abrocitinib had a faster onset of treatment benefit than dupilumab. However, treatment-emergent adverse events were more common with abrocitinib compared with dupilumab (74% vs 65%). Dupilumab was associated with more ocular adverse events (eg, conjunctivitis), whereas abrocitinib was associated with more headaches, nausea, and herpes zoster infections. These results provide important insights into the comparative effectiveness of treatments in moderate-to-severe AD. Of note, this study compared the higher dose of abrocitinib (200 mg) vs dupilumab. However, in the United States, the FDA-approved label recommends initiating abrocitinib therapy with the lower 100 mg dose and increasing to 200 mg only in those who had an inadequate response to 100 mg.
Additional References
1. Silverberg JI, Toth D, Bieber T, et al, for the ECZTRA 3 study investigators. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: Results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450-463. Doi: 10.1111/bjd.19573
2. Worm M, Simpson EL, Thaçi D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: A randomized clinical trial. JAMA Dermatol. 2020;156(2):131-143. Doi: 10.1001/jamadermatol.2019.3617
Let's start with tralokinumab. I previously had the privilege of being lead author on a study of the efficacy of tralokinumab beyond week 16 — the ECZTRA3 study.1 ECZTRA3 studied tralokinumab at the approved dose (600 mg loading dose followed by 300 mg every other week) vs placebo with concomitant topical corticosteroids (TCS) for an initial 16-week treatment period. Patients who achieved an Investigator's Global Assessment (IGA) score of 0 or 1 or 75% improvement in the Eczema Area and Severity Index (EASI-75) response were then randomly assigned again to receive 300 mg tralokinumab either continuously at every-other-week intervals or a prolonged interval of every 4 weeks (again with concomitant TCS).
With ECZTRA3, we found that patients continued to improve on tralokinumab + TCS well beyond week 16, with increased EASI-75 responses (week 16: 56%; week 32: 70.2%) and sustained or increased improvement across multiple patient-reported outcomes. Together, these results indicate that clinical responses may take more than 16 weeks to achieve with tralokinumab. In addition, some patients may be able to maintain clinical responses using fewer injections at 4-week intervals. This may allow tailoring dosing to individual patient needs. In fact, tralokinumab is approved in the United States and other regions with the option of every-2-week or every-4-week maintenance dosing in patients who have a good clinical response at week 16.
Since AD can be a lifelong disease, we expect that some patients will need to remain on various therapies for extended periods of time, perhaps many years, in order to maintain long-term control. It is imperative that any long-term treatment demonstrate a good long-term safety and efficacy profile. Blauvelt and colleagues published 2-year interim results from the ongoing ECZTEND long-term, open-label extension study of tralokinumab. They showed no new safety signals and stable rates of adverse events compared with earlier time points. Additionally, they showed that 82.5% of patients treated with open-label tralokinumab + TCS for 2 years maintained EASI-75 responses. These data are reassuring and support the potential use of tralokinumab as a long-term treatment option in AD.
While dupilumab is not approved for every-4-week maintenance dosing, a recent study by Spekhorst and colleagues confirmed that dupilumab can also be safely and effectively administered at intervals of every 4 weeks or every 6-8 weeks. Analyzing data from the BioDay real-world observational registry, they found that among patients who achieved good clinical responses (EASI scores ≤ 7) after 52 weeks of treatment with dupilumab administered every 2 weeks, many patients were able to maintain those responses at 3 months after the interval of administration was increased to every 4 weeks (> 80%) or 6-8 weeks (93.3%). These real-world data confirm the results previously observed in the phase 3 SOLO-CONTINUE study2 and support the use of maintenance dosing of dupilumab at prolonged intervals, though such use would technically be considered off-label.
Let’s also review some new data for abrocitinib, a once-daily oral preferential Janus kinase (JAK) 1 inhibitor. Reich and colleagues reported results from a phase 3 trial of adults with moderate-to-severe AD that compared the safety and efficacy of oral abrocitinib at the higher 200 mg dose vs subcutaneous dupilumab over 26 weeks. They found that more patients achieved ≥ 4-point improvement in the Peak Pruritus Numerical Rating Scale score at week 2 with 200 mg abrocitinib compared with 300 mg dupilumab every other week (48% vs 26%). There were also improved EASI-90 responses at week 4 (29% vs 15%). A dose of 200 mg abrocitinib was also significantly more effective than dupilumab for a number of additional investigator- and patient-reported outcomes. In general, abrocitinib had a faster onset of treatment benefit than dupilumab. However, treatment-emergent adverse events were more common with abrocitinib compared with dupilumab (74% vs 65%). Dupilumab was associated with more ocular adverse events (eg, conjunctivitis), whereas abrocitinib was associated with more headaches, nausea, and herpes zoster infections. These results provide important insights into the comparative effectiveness of treatments in moderate-to-severe AD. Of note, this study compared the higher dose of abrocitinib (200 mg) vs dupilumab. However, in the United States, the FDA-approved label recommends initiating abrocitinib therapy with the lower 100 mg dose and increasing to 200 mg only in those who had an inadequate response to 100 mg.
Additional References
1. Silverberg JI, Toth D, Bieber T, et al, for the ECZTRA 3 study investigators. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: Results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450-463. Doi: 10.1111/bjd.19573
2. Worm M, Simpson EL, Thaçi D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: A randomized clinical trial. JAMA Dermatol. 2020;156(2):131-143. Doi: 10.1001/jamadermatol.2019.3617
Let's start with tralokinumab. I previously had the privilege of being lead author on a study of the efficacy of tralokinumab beyond week 16 — the ECZTRA3 study.1 ECZTRA3 studied tralokinumab at the approved dose (600 mg loading dose followed by 300 mg every other week) vs placebo with concomitant topical corticosteroids (TCS) for an initial 16-week treatment period. Patients who achieved an Investigator's Global Assessment (IGA) score of 0 or 1 or 75% improvement in the Eczema Area and Severity Index (EASI-75) response were then randomly assigned again to receive 300 mg tralokinumab either continuously at every-other-week intervals or a prolonged interval of every 4 weeks (again with concomitant TCS).
With ECZTRA3, we found that patients continued to improve on tralokinumab + TCS well beyond week 16, with increased EASI-75 responses (week 16: 56%; week 32: 70.2%) and sustained or increased improvement across multiple patient-reported outcomes. Together, these results indicate that clinical responses may take more than 16 weeks to achieve with tralokinumab. In addition, some patients may be able to maintain clinical responses using fewer injections at 4-week intervals. This may allow tailoring dosing to individual patient needs. In fact, tralokinumab is approved in the United States and other regions with the option of every-2-week or every-4-week maintenance dosing in patients who have a good clinical response at week 16.
Since AD can be a lifelong disease, we expect that some patients will need to remain on various therapies for extended periods of time, perhaps many years, in order to maintain long-term control. It is imperative that any long-term treatment demonstrate a good long-term safety and efficacy profile. Blauvelt and colleagues published 2-year interim results from the ongoing ECZTEND long-term, open-label extension study of tralokinumab. They showed no new safety signals and stable rates of adverse events compared with earlier time points. Additionally, they showed that 82.5% of patients treated with open-label tralokinumab + TCS for 2 years maintained EASI-75 responses. These data are reassuring and support the potential use of tralokinumab as a long-term treatment option in AD.
While dupilumab is not approved for every-4-week maintenance dosing, a recent study by Spekhorst and colleagues confirmed that dupilumab can also be safely and effectively administered at intervals of every 4 weeks or every 6-8 weeks. Analyzing data from the BioDay real-world observational registry, they found that among patients who achieved good clinical responses (EASI scores ≤ 7) after 52 weeks of treatment with dupilumab administered every 2 weeks, many patients were able to maintain those responses at 3 months after the interval of administration was increased to every 4 weeks (> 80%) or 6-8 weeks (93.3%). These real-world data confirm the results previously observed in the phase 3 SOLO-CONTINUE study2 and support the use of maintenance dosing of dupilumab at prolonged intervals, though such use would technically be considered off-label.
Let’s also review some new data for abrocitinib, a once-daily oral preferential Janus kinase (JAK) 1 inhibitor. Reich and colleagues reported results from a phase 3 trial of adults with moderate-to-severe AD that compared the safety and efficacy of oral abrocitinib at the higher 200 mg dose vs subcutaneous dupilumab over 26 weeks. They found that more patients achieved ≥ 4-point improvement in the Peak Pruritus Numerical Rating Scale score at week 2 with 200 mg abrocitinib compared with 300 mg dupilumab every other week (48% vs 26%). There were also improved EASI-90 responses at week 4 (29% vs 15%). A dose of 200 mg abrocitinib was also significantly more effective than dupilumab for a number of additional investigator- and patient-reported outcomes. In general, abrocitinib had a faster onset of treatment benefit than dupilumab. However, treatment-emergent adverse events were more common with abrocitinib compared with dupilumab (74% vs 65%). Dupilumab was associated with more ocular adverse events (eg, conjunctivitis), whereas abrocitinib was associated with more headaches, nausea, and herpes zoster infections. These results provide important insights into the comparative effectiveness of treatments in moderate-to-severe AD. Of note, this study compared the higher dose of abrocitinib (200 mg) vs dupilumab. However, in the United States, the FDA-approved label recommends initiating abrocitinib therapy with the lower 100 mg dose and increasing to 200 mg only in those who had an inadequate response to 100 mg.
Additional References
1. Silverberg JI, Toth D, Bieber T, et al, for the ECZTRA 3 study investigators. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: Results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450-463. Doi: 10.1111/bjd.19573
2. Worm M, Simpson EL, Thaçi D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: A randomized clinical trial. JAMA Dermatol. 2020;156(2):131-143. Doi: 10.1001/jamadermatol.2019.3617
Commentary: Conditions Associated with AD, August 2022
In a cross-sectional observational study of 502 Finnish patients with AD, Salava and colleagues found that severe AD was associated with older age, male sex, early age of disease onset, higher body mass index, history of smoking, concomitant asthma, palmar hyperlinearity, hand dermatitis, history of contact allergy, and history of elevated immunoglobulin E levels. Some of these findings are correlated with each other. For example, palmar hyperlinearity was previously found to be a sign associated with early-onset AD in conjunction with Filaggrin loss-of-function mutations and atopic comorbidities.1,2 The association of AD with increased body mass index is consistent with previous studies that found associations of AD with overweight and obesity.3 In some instances, more severe AD may precede or lead to the association, eg, asthma and hand dermatitis. These results highlight the heterogeneity and complexity of AD, especially in moderate-to-severe disease.
AD is also associated with heterogeneous triggers. In clinical practice, we commonly see patients who consider food a potential trigger for AD. To better understand the role of food-triggered AD, Li and colleagues performed a retrospective study of 372 pediatric patients with AD. They found that more than half of the children with mild, moderate, and severe AD had an immunoglobulin E–mediated food allergy. Nevertheless, food-triggered AD occurred in only 3% of patients with AD. These results are doubly important because they indicate that clinicians should address food allergies to holistically improve the health of patients with AD. On the other hand, food is rarely a reproducible trigger of AD and appropriate treatment should generally not be withheld in favor of testing for food triggers of AD.
That said, it is important to address cutaneous and extra-cutaneous infections that occur in patients with AD to prevent worsening of AD and serious sequelae of infection. Indeed, Han and colleagues examined data from the Korean National Health Insurance Service, a nationwide population-based registry including 70,205 patients with AD and an unspecified number of control patients without AD. They found that AD was associated with significantly higher odds of molluscum contagiosum, impetigo, chickenpox, otitis media, eczema herpeticum, viral warts, and viral conjunctivitis. These results are consistent with previous studies from my research group showing higher rates of these and other infections.4-8 Anecdotally, I have seen all of these occur commonly in patients with AD, and in many instances these conditions worsen the underlying AD, eg, impetigo and eczema herpeticum.
The above-mentioned studies highlight the heterogeneity and complexity of AD, especially moderate-to-severe disease. Elsawi and colleagues conducted a survey-based study of 1065 adults with AD and found that moderate-to-severe AD was associated with increased patient burden, increased time spent managing AD symptoms, and comorbid depression. In addition, time spent managing AD symptoms was in and of itself a predictor of increased patient burden. These results underscore the many unmet needs that remain in the management of AD, with substantial patient burden from inadequate treatment as well as the inherent burden from the treatments themselves.
Additional References
1. Meng L, Wang L, Tang H, et al. Filaggrin gene mutation c.3321delA is associated with various clinical features of atopic dermatitis in the Chinese Han population. PloS One. 2014;9:e98235. Doi: 10.1371/journal.pone.0098235
2. Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219. Doi: 10.1016/j.jaci.2006.05.004
3. Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72:606-616.e4. Doi: 10.1016/j.jaad.2014.12.013
4. Narla S, Silverberg JI. Association between childhood atopic dermatitis and cutaneous, extracutaneous and systemic infections. Br J Dermatol. 2018;178:1467-1468. Doi: 10.1111/bjd.16482
5. Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Anb Allergy Asthma Immunol. 2018;120:66-72e11. Doi: 10.1016/j.anai.2017.10.019
6. Ren Z, Silverberg JI. Association of atopic dermatitis with bacterial, fungal, viral, and sexually transmitted skin infections. Dermatitis. 2020;31:157-164. Doi: 10.1097/DER.0000000000000526
7. Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Acad Am Acad Dermatol. 2019;80:904-912. Doi: 10.1016/j.jaad.2018.11.028
8. Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133:1041-1047. Doi: 10.1016/j.jaci.2013.08.012
In a cross-sectional observational study of 502 Finnish patients with AD, Salava and colleagues found that severe AD was associated with older age, male sex, early age of disease onset, higher body mass index, history of smoking, concomitant asthma, palmar hyperlinearity, hand dermatitis, history of contact allergy, and history of elevated immunoglobulin E levels. Some of these findings are correlated with each other. For example, palmar hyperlinearity was previously found to be a sign associated with early-onset AD in conjunction with Filaggrin loss-of-function mutations and atopic comorbidities.1,2 The association of AD with increased body mass index is consistent with previous studies that found associations of AD with overweight and obesity.3 In some instances, more severe AD may precede or lead to the association, eg, asthma and hand dermatitis. These results highlight the heterogeneity and complexity of AD, especially in moderate-to-severe disease.
AD is also associated with heterogeneous triggers. In clinical practice, we commonly see patients who consider food a potential trigger for AD. To better understand the role of food-triggered AD, Li and colleagues performed a retrospective study of 372 pediatric patients with AD. They found that more than half of the children with mild, moderate, and severe AD had an immunoglobulin E–mediated food allergy. Nevertheless, food-triggered AD occurred in only 3% of patients with AD. These results are doubly important because they indicate that clinicians should address food allergies to holistically improve the health of patients with AD. On the other hand, food is rarely a reproducible trigger of AD and appropriate treatment should generally not be withheld in favor of testing for food triggers of AD.
That said, it is important to address cutaneous and extra-cutaneous infections that occur in patients with AD to prevent worsening of AD and serious sequelae of infection. Indeed, Han and colleagues examined data from the Korean National Health Insurance Service, a nationwide population-based registry including 70,205 patients with AD and an unspecified number of control patients without AD. They found that AD was associated with significantly higher odds of molluscum contagiosum, impetigo, chickenpox, otitis media, eczema herpeticum, viral warts, and viral conjunctivitis. These results are consistent with previous studies from my research group showing higher rates of these and other infections.4-8 Anecdotally, I have seen all of these occur commonly in patients with AD, and in many instances these conditions worsen the underlying AD, eg, impetigo and eczema herpeticum.
The above-mentioned studies highlight the heterogeneity and complexity of AD, especially moderate-to-severe disease. Elsawi and colleagues conducted a survey-based study of 1065 adults with AD and found that moderate-to-severe AD was associated with increased patient burden, increased time spent managing AD symptoms, and comorbid depression. In addition, time spent managing AD symptoms was in and of itself a predictor of increased patient burden. These results underscore the many unmet needs that remain in the management of AD, with substantial patient burden from inadequate treatment as well as the inherent burden from the treatments themselves.
Additional References
1. Meng L, Wang L, Tang H, et al. Filaggrin gene mutation c.3321delA is associated with various clinical features of atopic dermatitis in the Chinese Han population. PloS One. 2014;9:e98235. Doi: 10.1371/journal.pone.0098235
2. Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219. Doi: 10.1016/j.jaci.2006.05.004
3. Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72:606-616.e4. Doi: 10.1016/j.jaad.2014.12.013
4. Narla S, Silverberg JI. Association between childhood atopic dermatitis and cutaneous, extracutaneous and systemic infections. Br J Dermatol. 2018;178:1467-1468. Doi: 10.1111/bjd.16482
5. Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Anb Allergy Asthma Immunol. 2018;120:66-72e11. Doi: 10.1016/j.anai.2017.10.019
6. Ren Z, Silverberg JI. Association of atopic dermatitis with bacterial, fungal, viral, and sexually transmitted skin infections. Dermatitis. 2020;31:157-164. Doi: 10.1097/DER.0000000000000526
7. Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Acad Am Acad Dermatol. 2019;80:904-912. Doi: 10.1016/j.jaad.2018.11.028
8. Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133:1041-1047. Doi: 10.1016/j.jaci.2013.08.012
In a cross-sectional observational study of 502 Finnish patients with AD, Salava and colleagues found that severe AD was associated with older age, male sex, early age of disease onset, higher body mass index, history of smoking, concomitant asthma, palmar hyperlinearity, hand dermatitis, history of contact allergy, and history of elevated immunoglobulin E levels. Some of these findings are correlated with each other. For example, palmar hyperlinearity was previously found to be a sign associated with early-onset AD in conjunction with Filaggrin loss-of-function mutations and atopic comorbidities.1,2 The association of AD with increased body mass index is consistent with previous studies that found associations of AD with overweight and obesity.3 In some instances, more severe AD may precede or lead to the association, eg, asthma and hand dermatitis. These results highlight the heterogeneity and complexity of AD, especially in moderate-to-severe disease.
AD is also associated with heterogeneous triggers. In clinical practice, we commonly see patients who consider food a potential trigger for AD. To better understand the role of food-triggered AD, Li and colleagues performed a retrospective study of 372 pediatric patients with AD. They found that more than half of the children with mild, moderate, and severe AD had an immunoglobulin E–mediated food allergy. Nevertheless, food-triggered AD occurred in only 3% of patients with AD. These results are doubly important because they indicate that clinicians should address food allergies to holistically improve the health of patients with AD. On the other hand, food is rarely a reproducible trigger of AD and appropriate treatment should generally not be withheld in favor of testing for food triggers of AD.
That said, it is important to address cutaneous and extra-cutaneous infections that occur in patients with AD to prevent worsening of AD and serious sequelae of infection. Indeed, Han and colleagues examined data from the Korean National Health Insurance Service, a nationwide population-based registry including 70,205 patients with AD and an unspecified number of control patients without AD. They found that AD was associated with significantly higher odds of molluscum contagiosum, impetigo, chickenpox, otitis media, eczema herpeticum, viral warts, and viral conjunctivitis. These results are consistent with previous studies from my research group showing higher rates of these and other infections.4-8 Anecdotally, I have seen all of these occur commonly in patients with AD, and in many instances these conditions worsen the underlying AD, eg, impetigo and eczema herpeticum.
The above-mentioned studies highlight the heterogeneity and complexity of AD, especially moderate-to-severe disease. Elsawi and colleagues conducted a survey-based study of 1065 adults with AD and found that moderate-to-severe AD was associated with increased patient burden, increased time spent managing AD symptoms, and comorbid depression. In addition, time spent managing AD symptoms was in and of itself a predictor of increased patient burden. These results underscore the many unmet needs that remain in the management of AD, with substantial patient burden from inadequate treatment as well as the inherent burden from the treatments themselves.
Additional References
1. Meng L, Wang L, Tang H, et al. Filaggrin gene mutation c.3321delA is associated with various clinical features of atopic dermatitis in the Chinese Han population. PloS One. 2014;9:e98235. Doi: 10.1371/journal.pone.0098235
2. Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219. Doi: 10.1016/j.jaci.2006.05.004
3. Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72:606-616.e4. Doi: 10.1016/j.jaad.2014.12.013
4. Narla S, Silverberg JI. Association between childhood atopic dermatitis and cutaneous, extracutaneous and systemic infections. Br J Dermatol. 2018;178:1467-1468. Doi: 10.1111/bjd.16482
5. Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Anb Allergy Asthma Immunol. 2018;120:66-72e11. Doi: 10.1016/j.anai.2017.10.019
6. Ren Z, Silverberg JI. Association of atopic dermatitis with bacterial, fungal, viral, and sexually transmitted skin infections. Dermatitis. 2020;31:157-164. Doi: 10.1097/DER.0000000000000526
7. Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Acad Am Acad Dermatol. 2019;80:904-912. Doi: 10.1016/j.jaad.2018.11.028
8. Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133:1041-1047. Doi: 10.1016/j.jaci.2013.08.012
Commentary: Support for the Use of Dupilumab in AD, and a Link Between AD and Depression, July 2022
First, Blauvelt and colleagues presented findings from the ongoing LIBERTY AD PED-OLE open-label extension study, including 294 adolescents with moderate to severe AD who participated in previous dupilumab trials. Patients received a maintenance dose of 300 mg dupilumab every 4 weeks, which was increased to a weight-based every-other-week regimen if there was inadequate clinical response to every-4-week dosing. They found that 81.2% of patients achieved an Eczema Area and Severity Index (EASI-75) response at week 52 with every-4-week dosing, and 51.9% of patients at week 48 after switching to every-2-week doing. These results indicate that some adolescents may be able to maintain clinical efficacy with monthly dosing, while others may require every-2-week dosing. Of note, no new safety signals emerged during the study and most adverse events were mild to moderate.
Two more studies were published showing real-world effectiveness and safety of dupilumab. Eichenfield and colleagues performed a retrospective, observational study of the effectiveness of dupilumab after 4 months of treatment using data from national electronic medical records in adults with moderate-to-severe AD. They found that most patients achieved at least a one-grade (81.8%) or two-grade (62.8%) improvement of their Investigator's Global Assessment (IGA) scores, with 42.8% achieving IGA scores of 0/1 (clear/minimal). There were also significant improvements in itch and lesional extent. The results were remarkably similar to those observed in the phase 3 clinical trial program of dupilumab in adults with moderate-to-severe AD.
Bagel and colleagues published baseline characteristics of patients enrolled in the ongoing PROSE longitudinal real-world registry of dupilumab use in adults with moderate-to-severe AD. Almost half of the patients (49.5%) previously received systemic medications, including 41.0% with systemic corticosteroids, 16.8% with nonsteroidal systemic therapies, such as cyclosporine and methotrexate, and 10.2% with phototherapy. This result indicates that many medical professionals are not using dupilumab as a first-line systemic therapy, despite its established record on safety and efficacy. It appears that many clinicians prefer a short-term treatment regimen, such as systemic corticosteroids, prior to initiating long-term treatment with dupilumab. However, short-term treatment approaches are not ideal for this chronic and often lifelong disease. It is important that clinicians develop appropriate long-term treatment approaches for atopic dermatitis in general, regardless of any specific therapy.
On a different research note, my research group just published the results of a longitudinal dermatology practice–based study of depressive symptoms in 695 adults with AD over time.1 We found that approximately half of the patients experienced fluctuating severity of depressive symptoms, and 45.65% experienced persistent severity of depression. Severity of AD lesions and itch were the strongest predictors of more severe symptoms of depression. Perhaps most fascinating about this research was that symptoms of depression improved dramatically in a very large subset of patients who experienced reduced AD severity with standard-of-care treatment. These results highlight the broader impacts of AD on mental health, which were recently recognized by the American Academy of Dermatology's guideline update on AD comorbidities.2 Moreover, our study demonstrated that many of these mental health impacts were modifiable with optimized AD therapy.
Additional References
1. Chatrath S, Lei D, Yousaf M, et al. vc Longitudinal course and predictors of depressive symptoms in atopic dermatitis. J Am Acad Dermatol. 2022 (May 9). Doi: 10.1016/j.jaad.2022.04.061
2. Davis DMR, Drucker AM, Alikhan A, et al. American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults. J Am Acad Dermatol. 2022;86:1335-1336.e18. Doi: 10.1016/j.jaad.2022.01.009
First, Blauvelt and colleagues presented findings from the ongoing LIBERTY AD PED-OLE open-label extension study, including 294 adolescents with moderate to severe AD who participated in previous dupilumab trials. Patients received a maintenance dose of 300 mg dupilumab every 4 weeks, which was increased to a weight-based every-other-week regimen if there was inadequate clinical response to every-4-week dosing. They found that 81.2% of patients achieved an Eczema Area and Severity Index (EASI-75) response at week 52 with every-4-week dosing, and 51.9% of patients at week 48 after switching to every-2-week doing. These results indicate that some adolescents may be able to maintain clinical efficacy with monthly dosing, while others may require every-2-week dosing. Of note, no new safety signals emerged during the study and most adverse events were mild to moderate.
Two more studies were published showing real-world effectiveness and safety of dupilumab. Eichenfield and colleagues performed a retrospective, observational study of the effectiveness of dupilumab after 4 months of treatment using data from national electronic medical records in adults with moderate-to-severe AD. They found that most patients achieved at least a one-grade (81.8%) or two-grade (62.8%) improvement of their Investigator's Global Assessment (IGA) scores, with 42.8% achieving IGA scores of 0/1 (clear/minimal). There were also significant improvements in itch and lesional extent. The results were remarkably similar to those observed in the phase 3 clinical trial program of dupilumab in adults with moderate-to-severe AD.
Bagel and colleagues published baseline characteristics of patients enrolled in the ongoing PROSE longitudinal real-world registry of dupilumab use in adults with moderate-to-severe AD. Almost half of the patients (49.5%) previously received systemic medications, including 41.0% with systemic corticosteroids, 16.8% with nonsteroidal systemic therapies, such as cyclosporine and methotrexate, and 10.2% with phototherapy. This result indicates that many medical professionals are not using dupilumab as a first-line systemic therapy, despite its established record on safety and efficacy. It appears that many clinicians prefer a short-term treatment regimen, such as systemic corticosteroids, prior to initiating long-term treatment with dupilumab. However, short-term treatment approaches are not ideal for this chronic and often lifelong disease. It is important that clinicians develop appropriate long-term treatment approaches for atopic dermatitis in general, regardless of any specific therapy.
On a different research note, my research group just published the results of a longitudinal dermatology practice–based study of depressive symptoms in 695 adults with AD over time.1 We found that approximately half of the patients experienced fluctuating severity of depressive symptoms, and 45.65% experienced persistent severity of depression. Severity of AD lesions and itch were the strongest predictors of more severe symptoms of depression. Perhaps most fascinating about this research was that symptoms of depression improved dramatically in a very large subset of patients who experienced reduced AD severity with standard-of-care treatment. These results highlight the broader impacts of AD on mental health, which were recently recognized by the American Academy of Dermatology's guideline update on AD comorbidities.2 Moreover, our study demonstrated that many of these mental health impacts were modifiable with optimized AD therapy.
Additional References
1. Chatrath S, Lei D, Yousaf M, et al. vc Longitudinal course and predictors of depressive symptoms in atopic dermatitis. J Am Acad Dermatol. 2022 (May 9). Doi: 10.1016/j.jaad.2022.04.061
2. Davis DMR, Drucker AM, Alikhan A, et al. American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults. J Am Acad Dermatol. 2022;86:1335-1336.e18. Doi: 10.1016/j.jaad.2022.01.009
First, Blauvelt and colleagues presented findings from the ongoing LIBERTY AD PED-OLE open-label extension study, including 294 adolescents with moderate to severe AD who participated in previous dupilumab trials. Patients received a maintenance dose of 300 mg dupilumab every 4 weeks, which was increased to a weight-based every-other-week regimen if there was inadequate clinical response to every-4-week dosing. They found that 81.2% of patients achieved an Eczema Area and Severity Index (EASI-75) response at week 52 with every-4-week dosing, and 51.9% of patients at week 48 after switching to every-2-week doing. These results indicate that some adolescents may be able to maintain clinical efficacy with monthly dosing, while others may require every-2-week dosing. Of note, no new safety signals emerged during the study and most adverse events were mild to moderate.
Two more studies were published showing real-world effectiveness and safety of dupilumab. Eichenfield and colleagues performed a retrospective, observational study of the effectiveness of dupilumab after 4 months of treatment using data from national electronic medical records in adults with moderate-to-severe AD. They found that most patients achieved at least a one-grade (81.8%) or two-grade (62.8%) improvement of their Investigator's Global Assessment (IGA) scores, with 42.8% achieving IGA scores of 0/1 (clear/minimal). There were also significant improvements in itch and lesional extent. The results were remarkably similar to those observed in the phase 3 clinical trial program of dupilumab in adults with moderate-to-severe AD.
Bagel and colleagues published baseline characteristics of patients enrolled in the ongoing PROSE longitudinal real-world registry of dupilumab use in adults with moderate-to-severe AD. Almost half of the patients (49.5%) previously received systemic medications, including 41.0% with systemic corticosteroids, 16.8% with nonsteroidal systemic therapies, such as cyclosporine and methotrexate, and 10.2% with phototherapy. This result indicates that many medical professionals are not using dupilumab as a first-line systemic therapy, despite its established record on safety and efficacy. It appears that many clinicians prefer a short-term treatment regimen, such as systemic corticosteroids, prior to initiating long-term treatment with dupilumab. However, short-term treatment approaches are not ideal for this chronic and often lifelong disease. It is important that clinicians develop appropriate long-term treatment approaches for atopic dermatitis in general, regardless of any specific therapy.
On a different research note, my research group just published the results of a longitudinal dermatology practice–based study of depressive symptoms in 695 adults with AD over time.1 We found that approximately half of the patients experienced fluctuating severity of depressive symptoms, and 45.65% experienced persistent severity of depression. Severity of AD lesions and itch were the strongest predictors of more severe symptoms of depression. Perhaps most fascinating about this research was that symptoms of depression improved dramatically in a very large subset of patients who experienced reduced AD severity with standard-of-care treatment. These results highlight the broader impacts of AD on mental health, which were recently recognized by the American Academy of Dermatology's guideline update on AD comorbidities.2 Moreover, our study demonstrated that many of these mental health impacts were modifiable with optimized AD therapy.
Additional References
1. Chatrath S, Lei D, Yousaf M, et al. vc Longitudinal course and predictors of depressive symptoms in atopic dermatitis. J Am Acad Dermatol. 2022 (May 9). Doi: 10.1016/j.jaad.2022.04.061
2. Davis DMR, Drucker AM, Alikhan A, et al. American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults. J Am Acad Dermatol. 2022;86:1335-1336.e18. Doi: 10.1016/j.jaad.2022.01.009
Commentary: Comparisons of Dupilumab and Other Atopic Dermatitis Treatments, June 2022
Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.
Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.
There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.
The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.
One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.
Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.
Additional References
1. Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi: 10.36849/JDD.6408
2. Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035
Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.
Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.
There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.
The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.
One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.
Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.
Additional References
1. Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi: 10.36849/JDD.6408
2. Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035
Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.
Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.
There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.
The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.
One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.
Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.
Additional References
1. Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi: 10.36849/JDD.6408
2. Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035
Clinical Edge Journal Scan Commentary: Atopic Dermatitis May 2022
- Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4-receptor alpha subunit. It was approved in the United States for the treatment of adults with moderate to severe AD in 2017 and has since been approved for children and adolescents down to 6 years of age. Ungar and colleagues studied the effects of dupilumab on SARS-CoV-2 antibody responses in patients with moderate to severe AD. They previously found that dupilumab was associated with milder COVID-19 illness. In this study, they similarly found that dupilumab was associated with lower immunoglobulin G (IgG) antibody levels to SARS-CoV-2, consistent with less severe COVID-19 illness. Future studies are needed to confirm these results. However, these results reassure that taking dupilumab does not pose any major harms in regard to COVID-19 outcomes.
- My patients with AD ask me on an almost daily basis about whether they should get vaccinated for SARS-CoV-2. I recommended that my patients get vaccinated, based on data from vaccine studies. However, there has been a dearth of data on the efficacy and safety of SARS-CoV-2 specifically in AD patients. Kridin and colleagues performed a population-based cohort study including 77,682 adults with AD, of which 58,582 patients had completed two doses of the BioNTech-Pfizer SARS-CoV-2 mRNA vaccine. They found that patients with AD who received both vs no vaccine doses had significantly lower risk for COVID-19, hospitalization, and mortality. These are the best data to date in support of SARS-CoV-2 vaccination in patients with AD. Of note, there was no significant impact of immunosuppressive drugs on vaccine efficacy against COVID-19. However, previous studies in other immune-mediated disorders suggest that immunosuppressants may lower vaccine immune responses.1,2 Some authors have advocated for temporarily discontinuing immunosuppressive agents for 1-2 weeks before and after administering SARS-CoV-2 vaccines. Currently, there is insufficient evidence to make strong recommendations.
Numerous in utero and early-life risk factors for AD have been examined over the years. Maternal stress and depression have been considered as potential risk factors for AD in children.
- My research group showed a while back that depression during pregnancy and in the postpartum period was associated with higher likelihood of AD in children.3
- Kawaguchi and colleagues recently analyzed data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan, including 8377 mother-child dyads where the child had not developed AD by the age of 1 year. They found that mothers with vs without psychological distress in both prenatal and postnatal periods or even only in the postnatal period had significantly increased risk of their children developing AD at 1-2 years of age. It seems prudent that mothers try to minimize stress during pregnancy and postpartum, though, understandably, this is not always feasible. Additionally, children of mothers who experience a lot of stress during pregnancy or postpartum may benefit from closer surveillance for the development of AD and other atopic diseases.
Additional References
1. Dayam RM, Law JC, Goetbebuer RL, et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases. JCI Insight. 2022 (Apr 26). Doi: 10.1172/jci.insight.159721 Source
2. Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. 2022;81:710-719. Doi: 10.1136/annrheumdis-2021-221735 Source
3. McKenzie C, Silverberg JI. Maternal depression and atopic dermatitis in American children and adolescents. Dermatitis. 2020;31:75-80. Doi: 10.1097/DER.0000000000000548 Source
- Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4-receptor alpha subunit. It was approved in the United States for the treatment of adults with moderate to severe AD in 2017 and has since been approved for children and adolescents down to 6 years of age. Ungar and colleagues studied the effects of dupilumab on SARS-CoV-2 antibody responses in patients with moderate to severe AD. They previously found that dupilumab was associated with milder COVID-19 illness. In this study, they similarly found that dupilumab was associated with lower immunoglobulin G (IgG) antibody levels to SARS-CoV-2, consistent with less severe COVID-19 illness. Future studies are needed to confirm these results. However, these results reassure that taking dupilumab does not pose any major harms in regard to COVID-19 outcomes.
- My patients with AD ask me on an almost daily basis about whether they should get vaccinated for SARS-CoV-2. I recommended that my patients get vaccinated, based on data from vaccine studies. However, there has been a dearth of data on the efficacy and safety of SARS-CoV-2 specifically in AD patients. Kridin and colleagues performed a population-based cohort study including 77,682 adults with AD, of which 58,582 patients had completed two doses of the BioNTech-Pfizer SARS-CoV-2 mRNA vaccine. They found that patients with AD who received both vs no vaccine doses had significantly lower risk for COVID-19, hospitalization, and mortality. These are the best data to date in support of SARS-CoV-2 vaccination in patients with AD. Of note, there was no significant impact of immunosuppressive drugs on vaccine efficacy against COVID-19. However, previous studies in other immune-mediated disorders suggest that immunosuppressants may lower vaccine immune responses.1,2 Some authors have advocated for temporarily discontinuing immunosuppressive agents for 1-2 weeks before and after administering SARS-CoV-2 vaccines. Currently, there is insufficient evidence to make strong recommendations.
Numerous in utero and early-life risk factors for AD have been examined over the years. Maternal stress and depression have been considered as potential risk factors for AD in children.
- My research group showed a while back that depression during pregnancy and in the postpartum period was associated with higher likelihood of AD in children.3
- Kawaguchi and colleagues recently analyzed data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan, including 8377 mother-child dyads where the child had not developed AD by the age of 1 year. They found that mothers with vs without psychological distress in both prenatal and postnatal periods or even only in the postnatal period had significantly increased risk of their children developing AD at 1-2 years of age. It seems prudent that mothers try to minimize stress during pregnancy and postpartum, though, understandably, this is not always feasible. Additionally, children of mothers who experience a lot of stress during pregnancy or postpartum may benefit from closer surveillance for the development of AD and other atopic diseases.
Additional References
1. Dayam RM, Law JC, Goetbebuer RL, et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases. JCI Insight. 2022 (Apr 26). Doi: 10.1172/jci.insight.159721 Source
2. Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. 2022;81:710-719. Doi: 10.1136/annrheumdis-2021-221735 Source
3. McKenzie C, Silverberg JI. Maternal depression and atopic dermatitis in American children and adolescents. Dermatitis. 2020;31:75-80. Doi: 10.1097/DER.0000000000000548 Source
- Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4-receptor alpha subunit. It was approved in the United States for the treatment of adults with moderate to severe AD in 2017 and has since been approved for children and adolescents down to 6 years of age. Ungar and colleagues studied the effects of dupilumab on SARS-CoV-2 antibody responses in patients with moderate to severe AD. They previously found that dupilumab was associated with milder COVID-19 illness. In this study, they similarly found that dupilumab was associated with lower immunoglobulin G (IgG) antibody levels to SARS-CoV-2, consistent with less severe COVID-19 illness. Future studies are needed to confirm these results. However, these results reassure that taking dupilumab does not pose any major harms in regard to COVID-19 outcomes.
- My patients with AD ask me on an almost daily basis about whether they should get vaccinated for SARS-CoV-2. I recommended that my patients get vaccinated, based on data from vaccine studies. However, there has been a dearth of data on the efficacy and safety of SARS-CoV-2 specifically in AD patients. Kridin and colleagues performed a population-based cohort study including 77,682 adults with AD, of which 58,582 patients had completed two doses of the BioNTech-Pfizer SARS-CoV-2 mRNA vaccine. They found that patients with AD who received both vs no vaccine doses had significantly lower risk for COVID-19, hospitalization, and mortality. These are the best data to date in support of SARS-CoV-2 vaccination in patients with AD. Of note, there was no significant impact of immunosuppressive drugs on vaccine efficacy against COVID-19. However, previous studies in other immune-mediated disorders suggest that immunosuppressants may lower vaccine immune responses.1,2 Some authors have advocated for temporarily discontinuing immunosuppressive agents for 1-2 weeks before and after administering SARS-CoV-2 vaccines. Currently, there is insufficient evidence to make strong recommendations.
Numerous in utero and early-life risk factors for AD have been examined over the years. Maternal stress and depression have been considered as potential risk factors for AD in children.
- My research group showed a while back that depression during pregnancy and in the postpartum period was associated with higher likelihood of AD in children.3
- Kawaguchi and colleagues recently analyzed data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan, including 8377 mother-child dyads where the child had not developed AD by the age of 1 year. They found that mothers with vs without psychological distress in both prenatal and postnatal periods or even only in the postnatal period had significantly increased risk of their children developing AD at 1-2 years of age. It seems prudent that mothers try to minimize stress during pregnancy and postpartum, though, understandably, this is not always feasible. Additionally, children of mothers who experience a lot of stress during pregnancy or postpartum may benefit from closer surveillance for the development of AD and other atopic diseases.
Additional References
1. Dayam RM, Law JC, Goetbebuer RL, et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases. JCI Insight. 2022 (Apr 26). Doi: 10.1172/jci.insight.159721 Source
2. Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. 2022;81:710-719. Doi: 10.1136/annrheumdis-2021-221735 Source
3. McKenzie C, Silverberg JI. Maternal depression and atopic dermatitis in American children and adolescents. Dermatitis. 2020;31:75-80. Doi: 10.1097/DER.0000000000000548 Source
Clinical Edge Journal Scan Commentary: Atopic Dermatitis April 2022
Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4 receptor alpha subunit. It has been approved in the United States for the treatment of adults with moderate-to-severe AD since 2017 and has since been approved for children and adolescents older than 6 years. Many real-world studies of the effectiveness of dupilumab have been published over the past few years. Kojanova and colleagues reported findings from a retrospective, multicenter study of 360 adults with severe AD who received dupilumab. They found that a high proportion of patients achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16 (66.6%), 1 year (89.5%), and 2 years (95.8%). Drug persistence rates were very high (> 90%) throughout the 2 years of therapy, suggesting that dupilumab was effective and well-tolerated.
Dupilumab was previously found to be associated with increased conjunctivitis in clinical trials and real-world studies. Schneeweiss and colleagues conducted a population-based longitudinal study of 5,004,117 patients with AD who newly initiated dupilumab, methotrexate, mycophenolate, and cyclosporine. They found that the risk of developing conjunctivitis diagnosed in clinical practice within 6 months of treatment initiation was approximately double with dupilumab compared with methotrexate, mycophenolate, or cyclosporine. Interestingly, comorbid asthma was found to be a risk factor for conjunctivitis in dupilumab initiators. This study provides insight into how commonly clinically significant conjunctivitis occurs with dupilumab treatment. Of note, the study results may underestimate the incidence of conjunctivitis because milder cases may go undetected.
Upadacitinib is an oral selective Janus kinase (JAK) 1 inhibitor that was approved in the United States in 2022 for the treatment of moderate-to-severe AD. Simpson and colleagues reported on the long-term efficacy and safety of oral upadacitinib from the phase 3 double-blind, randomized controlled trials Measure Up 1 and Measure Up 2 in adolescents and adults with moderate-to-severe atopic dermatitis ho had an inadequate response to topical therapy. The initial phase of the Measure Up 1 and Measure Up 2 studies was 16 weeks in duration, with a placebo control group. At week 16, patients who received 15 or 30 mg upadacitinib in the initial 16 weeks of the study continued to receive that dose. Patients who received placebo in the initial 16 weeks were randomly assigned to receive oral 15 mg or 30 mg upadacitinib daily. So, in the long run, all patients received upadacitinib in the second phase of the study but were blinded to the dose they were receiving. The results from the first 16 weeks of treatment were previously published. Simpson and colleagues reported on the results up to week 52 from the second phase of the study. They showed that at week 52, 82.0% and 79.1% of patients in Measure Up 1 and Measure Up 2 achieved a 75% improvement in EASI-75 when continuing on 15 mg upadacitinib and 84.9% and 84.3% in patients continuing 30 mg upadacitinib, respectively. More than 80% of patients who switched from placebo to upadacitinib at week 16 achieved EASI-75 at week 52. No safety signals were observed in this phase of the study that were not previously observed in other studies of upadacitinib for atopic dermatitis and other indications (rheumatoid arthritis and psoriatic arthritis). These results indicate that upadacitinib has durable efficacy with long-term treatment in moderate-to-severe AD. These studies are ongoing, and I look forward to future results reporting for even longer-term treatment.
It is an exciting time in dermatology with the arrival of multiple novel therapies for atopic dermatitis. The field has already benefited so much by the tremendous interest and research effort into understanding how to best manage this disease. With so many more treatments in the pipeline, perhaps the best is yet to come.
Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4 receptor alpha subunit. It has been approved in the United States for the treatment of adults with moderate-to-severe AD since 2017 and has since been approved for children and adolescents older than 6 years. Many real-world studies of the effectiveness of dupilumab have been published over the past few years. Kojanova and colleagues reported findings from a retrospective, multicenter study of 360 adults with severe AD who received dupilumab. They found that a high proportion of patients achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16 (66.6%), 1 year (89.5%), and 2 years (95.8%). Drug persistence rates were very high (> 90%) throughout the 2 years of therapy, suggesting that dupilumab was effective and well-tolerated.
Dupilumab was previously found to be associated with increased conjunctivitis in clinical trials and real-world studies. Schneeweiss and colleagues conducted a population-based longitudinal study of 5,004,117 patients with AD who newly initiated dupilumab, methotrexate, mycophenolate, and cyclosporine. They found that the risk of developing conjunctivitis diagnosed in clinical practice within 6 months of treatment initiation was approximately double with dupilumab compared with methotrexate, mycophenolate, or cyclosporine. Interestingly, comorbid asthma was found to be a risk factor for conjunctivitis in dupilumab initiators. This study provides insight into how commonly clinically significant conjunctivitis occurs with dupilumab treatment. Of note, the study results may underestimate the incidence of conjunctivitis because milder cases may go undetected.
Upadacitinib is an oral selective Janus kinase (JAK) 1 inhibitor that was approved in the United States in 2022 for the treatment of moderate-to-severe AD. Simpson and colleagues reported on the long-term efficacy and safety of oral upadacitinib from the phase 3 double-blind, randomized controlled trials Measure Up 1 and Measure Up 2 in adolescents and adults with moderate-to-severe atopic dermatitis ho had an inadequate response to topical therapy. The initial phase of the Measure Up 1 and Measure Up 2 studies was 16 weeks in duration, with a placebo control group. At week 16, patients who received 15 or 30 mg upadacitinib in the initial 16 weeks of the study continued to receive that dose. Patients who received placebo in the initial 16 weeks were randomly assigned to receive oral 15 mg or 30 mg upadacitinib daily. So, in the long run, all patients received upadacitinib in the second phase of the study but were blinded to the dose they were receiving. The results from the first 16 weeks of treatment were previously published. Simpson and colleagues reported on the results up to week 52 from the second phase of the study. They showed that at week 52, 82.0% and 79.1% of patients in Measure Up 1 and Measure Up 2 achieved a 75% improvement in EASI-75 when continuing on 15 mg upadacitinib and 84.9% and 84.3% in patients continuing 30 mg upadacitinib, respectively. More than 80% of patients who switched from placebo to upadacitinib at week 16 achieved EASI-75 at week 52. No safety signals were observed in this phase of the study that were not previously observed in other studies of upadacitinib for atopic dermatitis and other indications (rheumatoid arthritis and psoriatic arthritis). These results indicate that upadacitinib has durable efficacy with long-term treatment in moderate-to-severe AD. These studies are ongoing, and I look forward to future results reporting for even longer-term treatment.
It is an exciting time in dermatology with the arrival of multiple novel therapies for atopic dermatitis. The field has already benefited so much by the tremendous interest and research effort into understanding how to best manage this disease. With so many more treatments in the pipeline, perhaps the best is yet to come.
Dupilumab is a subcutaneous injection therapy that inhibits the interleukin 4 receptor alpha subunit. It has been approved in the United States for the treatment of adults with moderate-to-severe AD since 2017 and has since been approved for children and adolescents older than 6 years. Many real-world studies of the effectiveness of dupilumab have been published over the past few years. Kojanova and colleagues reported findings from a retrospective, multicenter study of 360 adults with severe AD who received dupilumab. They found that a high proportion of patients achieved a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16 (66.6%), 1 year (89.5%), and 2 years (95.8%). Drug persistence rates were very high (> 90%) throughout the 2 years of therapy, suggesting that dupilumab was effective and well-tolerated.
Dupilumab was previously found to be associated with increased conjunctivitis in clinical trials and real-world studies. Schneeweiss and colleagues conducted a population-based longitudinal study of 5,004,117 patients with AD who newly initiated dupilumab, methotrexate, mycophenolate, and cyclosporine. They found that the risk of developing conjunctivitis diagnosed in clinical practice within 6 months of treatment initiation was approximately double with dupilumab compared with methotrexate, mycophenolate, or cyclosporine. Interestingly, comorbid asthma was found to be a risk factor for conjunctivitis in dupilumab initiators. This study provides insight into how commonly clinically significant conjunctivitis occurs with dupilumab treatment. Of note, the study results may underestimate the incidence of conjunctivitis because milder cases may go undetected.
Upadacitinib is an oral selective Janus kinase (JAK) 1 inhibitor that was approved in the United States in 2022 for the treatment of moderate-to-severe AD. Simpson and colleagues reported on the long-term efficacy and safety of oral upadacitinib from the phase 3 double-blind, randomized controlled trials Measure Up 1 and Measure Up 2 in adolescents and adults with moderate-to-severe atopic dermatitis ho had an inadequate response to topical therapy. The initial phase of the Measure Up 1 and Measure Up 2 studies was 16 weeks in duration, with a placebo control group. At week 16, patients who received 15 or 30 mg upadacitinib in the initial 16 weeks of the study continued to receive that dose. Patients who received placebo in the initial 16 weeks were randomly assigned to receive oral 15 mg or 30 mg upadacitinib daily. So, in the long run, all patients received upadacitinib in the second phase of the study but were blinded to the dose they were receiving. The results from the first 16 weeks of treatment were previously published. Simpson and colleagues reported on the results up to week 52 from the second phase of the study. They showed that at week 52, 82.0% and 79.1% of patients in Measure Up 1 and Measure Up 2 achieved a 75% improvement in EASI-75 when continuing on 15 mg upadacitinib and 84.9% and 84.3% in patients continuing 30 mg upadacitinib, respectively. More than 80% of patients who switched from placebo to upadacitinib at week 16 achieved EASI-75 at week 52. No safety signals were observed in this phase of the study that were not previously observed in other studies of upadacitinib for atopic dermatitis and other indications (rheumatoid arthritis and psoriatic arthritis). These results indicate that upadacitinib has durable efficacy with long-term treatment in moderate-to-severe AD. These studies are ongoing, and I look forward to future results reporting for even longer-term treatment.
It is an exciting time in dermatology with the arrival of multiple novel therapies for atopic dermatitis. The field has already benefited so much by the tremendous interest and research effort into understanding how to best manage this disease. With so many more treatments in the pipeline, perhaps the best is yet to come.
Clinical Edge Journal Scan Commentary: Atopic Dermatitis March 2022
Recent insights into the epidemiology of atopic dermatitis
Atopic dermatitis (AD) has complex risk factors and effects on patients. AD patients experience itch, skin pain, sleep disturbances, and other symptoms that can profoundly impact their quality of life. Yet, little is known about the longitudinal epidemiology and burden of AD in children.
- Johansson et al1 reported on the ongoing BAMSE cohort study. BAMSE followed 4089 individuals regularly from birth regarding AD and atopic diseases with surveys and clinical examinations; 3055 individuals were assessed at year 24 of follow-up. At 24 years, the 12-month prevalence of AD was 17.8% and more common in women than men (20.5% vs. 14.8%). The point prevalence of AD on clinical examination was 8.0%. These high prevalence estimates are consistent with multiple other recent studies in the United States and globally.2-4 Prevalence measures a combination of both new-onset (incident) cases and persistence of childhood disease. Importantly, BAMSE found the proportion of adult-onset AD was 16.9%. These results are consistent with previous studies that found substantial rates of adult-onset AD.5 Additionally, men were more likely to have AD in the first year of life, but less likely than women to have AD in adolescence and young adulthood.
- Paller et al6 recently initiated PEDISTAT, an international, longitudinal 5-year registry of the disease course, comorbidities, treatment, and disease burden children age <12 years with moderate-severe AD. While the study is ongoing, the authors reported the baseline characteristics of the registry. They found that most of the enrolled children were not treated with a systemic therapy, had inadequately controlled disease and a high disease burden. These results emphasize the need for very safe and highly effective systemic therapies for moderate-severe AD in children.
I look forward to seeing the results of these ongoing study and how they will inform our understanding of the epidemiology and comorbidities of AD.
Numerous risk factors for AD have been examined. Infections have been explored as a potential risk factor for AD for more than 30 years.
- Lin et al7 conducted a population-based, nationwide case-control study including 5,454 children with AD matched with 16,362 healthy controls without AD. They found that prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in children who subsequently developed AD compared to healthy controls.
- Medeleanu et al8 reported findings from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which included a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy. They found that infants with moderate-severe vs. no or mild lower respiratory tract infections in the first 18 months of life had significantly higher rates of AD and type 1 allergen polysensitization at age 3 and 5 years. These associations remained significant after adjusting for sex, breastfeeding duration, and parental history of atopy or asthma.
Together, these studies suggest that prevention and expedient treatment of early life infections may lower risk for AD in childhood. Conversely, children at risk for AD who experience certain infections early in life may benefit from increased surveillance for AD and atopic disease.
References
- Johansson EK et al. Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE. J Eur Acad Dermatol Venereol. 2022 (Jan 15).
- Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283-289.
- Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study. Ann Allerg Asthma Immunol. 2018;121(3):340-347.
- Hua T, Silverberg JI. Atopic dermatitis in US adults: Epidemiology, association with marital status, and atopy. Ann Allerg Asthma Immunol. 2018;121(5):622-624.
- Lee HH et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e7.
- Paller AS et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022 (Jan 26).
- Lin T-L et al. Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case–control study. J Eur Acad Dermatol Venereol. 2022 (Jan 9).
- Medeleanu M et al. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study. J Allergy Clin Immunol. 2022 (Jan 16).
Recent insights into the epidemiology of atopic dermatitis
Atopic dermatitis (AD) has complex risk factors and effects on patients. AD patients experience itch, skin pain, sleep disturbances, and other symptoms that can profoundly impact their quality of life. Yet, little is known about the longitudinal epidemiology and burden of AD in children.
- Johansson et al1 reported on the ongoing BAMSE cohort study. BAMSE followed 4089 individuals regularly from birth regarding AD and atopic diseases with surveys and clinical examinations; 3055 individuals were assessed at year 24 of follow-up. At 24 years, the 12-month prevalence of AD was 17.8% and more common in women than men (20.5% vs. 14.8%). The point prevalence of AD on clinical examination was 8.0%. These high prevalence estimates are consistent with multiple other recent studies in the United States and globally.2-4 Prevalence measures a combination of both new-onset (incident) cases and persistence of childhood disease. Importantly, BAMSE found the proportion of adult-onset AD was 16.9%. These results are consistent with previous studies that found substantial rates of adult-onset AD.5 Additionally, men were more likely to have AD in the first year of life, but less likely than women to have AD in adolescence and young adulthood.
- Paller et al6 recently initiated PEDISTAT, an international, longitudinal 5-year registry of the disease course, comorbidities, treatment, and disease burden children age <12 years with moderate-severe AD. While the study is ongoing, the authors reported the baseline characteristics of the registry. They found that most of the enrolled children were not treated with a systemic therapy, had inadequately controlled disease and a high disease burden. These results emphasize the need for very safe and highly effective systemic therapies for moderate-severe AD in children.
I look forward to seeing the results of these ongoing study and how they will inform our understanding of the epidemiology and comorbidities of AD.
Numerous risk factors for AD have been examined. Infections have been explored as a potential risk factor for AD for more than 30 years.
- Lin et al7 conducted a population-based, nationwide case-control study including 5,454 children with AD matched with 16,362 healthy controls without AD. They found that prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in children who subsequently developed AD compared to healthy controls.
- Medeleanu et al8 reported findings from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which included a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy. They found that infants with moderate-severe vs. no or mild lower respiratory tract infections in the first 18 months of life had significantly higher rates of AD and type 1 allergen polysensitization at age 3 and 5 years. These associations remained significant after adjusting for sex, breastfeeding duration, and parental history of atopy or asthma.
Together, these studies suggest that prevention and expedient treatment of early life infections may lower risk for AD in childhood. Conversely, children at risk for AD who experience certain infections early in life may benefit from increased surveillance for AD and atopic disease.
References
- Johansson EK et al. Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE. J Eur Acad Dermatol Venereol. 2022 (Jan 15).
- Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283-289.
- Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study. Ann Allerg Asthma Immunol. 2018;121(3):340-347.
- Hua T, Silverberg JI. Atopic dermatitis in US adults: Epidemiology, association with marital status, and atopy. Ann Allerg Asthma Immunol. 2018;121(5):622-624.
- Lee HH et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e7.
- Paller AS et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022 (Jan 26).
- Lin T-L et al. Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case–control study. J Eur Acad Dermatol Venereol. 2022 (Jan 9).
- Medeleanu M et al. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study. J Allergy Clin Immunol. 2022 (Jan 16).
Recent insights into the epidemiology of atopic dermatitis
Atopic dermatitis (AD) has complex risk factors and effects on patients. AD patients experience itch, skin pain, sleep disturbances, and other symptoms that can profoundly impact their quality of life. Yet, little is known about the longitudinal epidemiology and burden of AD in children.
- Johansson et al1 reported on the ongoing BAMSE cohort study. BAMSE followed 4089 individuals regularly from birth regarding AD and atopic diseases with surveys and clinical examinations; 3055 individuals were assessed at year 24 of follow-up. At 24 years, the 12-month prevalence of AD was 17.8% and more common in women than men (20.5% vs. 14.8%). The point prevalence of AD on clinical examination was 8.0%. These high prevalence estimates are consistent with multiple other recent studies in the United States and globally.2-4 Prevalence measures a combination of both new-onset (incident) cases and persistence of childhood disease. Importantly, BAMSE found the proportion of adult-onset AD was 16.9%. These results are consistent with previous studies that found substantial rates of adult-onset AD.5 Additionally, men were more likely to have AD in the first year of life, but less likely than women to have AD in adolescence and young adulthood.
- Paller et al6 recently initiated PEDISTAT, an international, longitudinal 5-year registry of the disease course, comorbidities, treatment, and disease burden children age <12 years with moderate-severe AD. While the study is ongoing, the authors reported the baseline characteristics of the registry. They found that most of the enrolled children were not treated with a systemic therapy, had inadequately controlled disease and a high disease burden. These results emphasize the need for very safe and highly effective systemic therapies for moderate-severe AD in children.
I look forward to seeing the results of these ongoing study and how they will inform our understanding of the epidemiology and comorbidities of AD.
Numerous risk factors for AD have been examined. Infections have been explored as a potential risk factor for AD for more than 30 years.
- Lin et al7 conducted a population-based, nationwide case-control study including 5,454 children with AD matched with 16,362 healthy controls without AD. They found that prior to AD diagnosis, all infections including skin infection up to 2 years of age were more frequent in children who subsequently developed AD compared to healthy controls.
- Medeleanu et al8 reported findings from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study, which included a longitudinal birth cohort of 3,272 parents and infants recruited during pregnancy. They found that infants with moderate-severe vs. no or mild lower respiratory tract infections in the first 18 months of life had significantly higher rates of AD and type 1 allergen polysensitization at age 3 and 5 years. These associations remained significant after adjusting for sex, breastfeeding duration, and parental history of atopy or asthma.
Together, these studies suggest that prevention and expedient treatment of early life infections may lower risk for AD in childhood. Conversely, children at risk for AD who experience certain infections early in life may benefit from increased surveillance for AD and atopic disease.
References
- Johansson EK et al. Prevalence and characteristics of atopic dermatitis among young adult females and males-report from the Swedish population-based study BAMSE. J Eur Acad Dermatol Venereol. 2022 (Jan 15).
- Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 2017;35(3):283-289.
- Silverberg JI et al. Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study. Ann Allerg Asthma Immunol. 2018;121(3):340-347.
- Hua T, Silverberg JI. Atopic dermatitis in US adults: Epidemiology, association with marital status, and atopy. Ann Allerg Asthma Immunol. 2018;121(5):622-624.
- Lee HH et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis. J Am Acad Dermatol. 2019;80(6):1526-1532.e7.
- Paller AS et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022 (Jan 26).
- Lin T-L et al. Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case–control study. J Eur Acad Dermatol Venereol. 2022 (Jan 9).
- Medeleanu M et al. Moderate-to-severe lower respiratory tract infection in early life is associated with increased risk of polysensitization and atopic dermatitis: Findings from the CHILD Study. J Allergy Clin Immunol. 2022 (Jan 16).