Atopic Dermatitis

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

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

Key clinical point: Atopic dermatitis (AD) had a detrimental impact on the families of pediatric patients, with not only severe AD but even mild AD having a substantial impact on family life.

Major finding: There was a substantial impact of AD on families across geographic regions, as assessed by Dermatitis Family Impact (DFI) score, which increased with the severity of AD (mild: 3.3-11.3, moderate: 6.9-17.1, and severe: 11-20.3). A DFI score of >9.6 was reported for 37.2%, 70.7%, and 78.0% of patients with mild, moderate, and severe AD, respectively.

Study details: Findings are from the cross-sectional, web-based survey including 7465 pairs of pediatric patients with AD and their parents/caregivers.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals Inc. Five authors declared being current or former employees or stockholders of Sanofi or Regeneron Pharmaceuticals, and some others declared ties with various sources.

Source: Barbarot S et al. The family impact of atopic dermatitis in the pediatric population: Results from an international cross-sectional study. J Pediatr. 2022 (Apr 28). Doi: 10.1016/j.jpeds.2022.04.027

Key clinical point: Atopic dermatitis (AD) had a detrimental impact on the families of pediatric patients, with not only severe AD but even mild AD having a substantial impact on family life.

Major finding: There was a substantial impact of AD on families across geographic regions, as assessed by Dermatitis Family Impact (DFI) score, which increased with the severity of AD (mild: 3.3-11.3, moderate: 6.9-17.1, and severe: 11-20.3). A DFI score of >9.6 was reported for 37.2%, 70.7%, and 78.0% of patients with mild, moderate, and severe AD, respectively.

Study details: Findings are from the cross-sectional, web-based survey including 7465 pairs of pediatric patients with AD and their parents/caregivers.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals Inc. Five authors declared being current or former employees or stockholders of Sanofi or Regeneron Pharmaceuticals, and some others declared ties with various sources.

Source: Barbarot S et al. The family impact of atopic dermatitis in the pediatric population: Results from an international cross-sectional study. J Pediatr. 2022 (Apr 28). Doi: 10.1016/j.jpeds.2022.04.027

Key clinical point: Atopic dermatitis (AD) had a detrimental impact on the families of pediatric patients, with not only severe AD but even mild AD having a substantial impact on family life.

Major finding: There was a substantial impact of AD on families across geographic regions, as assessed by Dermatitis Family Impact (DFI) score, which increased with the severity of AD (mild: 3.3-11.3, moderate: 6.9-17.1, and severe: 11-20.3). A DFI score of >9.6 was reported for 37.2%, 70.7%, and 78.0% of patients with mild, moderate, and severe AD, respectively.

Study details: Findings are from the cross-sectional, web-based survey including 7465 pairs of pediatric patients with AD and their parents/caregivers.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals Inc. Five authors declared being current or former employees or stockholders of Sanofi or Regeneron Pharmaceuticals, and some others declared ties with various sources.

Source: Barbarot S et al. The family impact of atopic dermatitis in the pediatric population: Results from an international cross-sectional study. J Pediatr. 2022 (Apr 28). Doi: 10.1016/j.jpeds.2022.04.027

Key clinical point: Children diagnosed with atopic dermatitis (AD) within the first 10 years of life are more likely to develop a more proinflammatory dietary pattern and consume less fiber and several vitamins, which may worsen the atopic outcome itself.

Major finding: The intake of fiber (P = .04), vitamin C (P = .02), vitamin E (P = .03), and vitamin B₇ (biotin) (P = .047) were significantly lower among children who developed vs did not develop AD in the first 10 years of life, with a significant association observed between presence of AD and a proinflammatory dietary pattern at 10 years of age (odds ratio 2.22; P = .02).

Study details: Findings are from the population-based LiNA cohort study including 211 10-year-old children.

Disclosures: This LiNA study was funded by the Department of Environmental Immunology, Helmholtz Centre for Environmental Research. JR Hebert declared owning controlling interest in Connecting Health Innovations LLC.

Source: Schütte O et al. Pro-inflammatory diet pictured in children with atopic dermatitis or food allergy: Nutritional data of the LiNA cohort. Front Nutr. 2022;9:868872 (Apr 8). Doi: 10.3389/fnut.2022.868872

Key clinical point: Children diagnosed with atopic dermatitis (AD) within the first 10 years of life are more likely to develop a more proinflammatory dietary pattern and consume less fiber and several vitamins, which may worsen the atopic outcome itself.

Major finding: The intake of fiber (P = .04), vitamin C (P = .02), vitamin E (P = .03), and vitamin B₇ (biotin) (P = .047) were significantly lower among children who developed vs did not develop AD in the first 10 years of life, with a significant association observed between presence of AD and a proinflammatory dietary pattern at 10 years of age (odds ratio 2.22; P = .02).

Study details: Findings are from the population-based LiNA cohort study including 211 10-year-old children.

Disclosures: This LiNA study was funded by the Department of Environmental Immunology, Helmholtz Centre for Environmental Research. JR Hebert declared owning controlling interest in Connecting Health Innovations LLC.

Source: Schütte O et al. Pro-inflammatory diet pictured in children with atopic dermatitis or food allergy: Nutritional data of the LiNA cohort. Front Nutr. 2022;9:868872 (Apr 8). Doi: 10.3389/fnut.2022.868872

Key clinical point: Children diagnosed with atopic dermatitis (AD) within the first 10 years of life are more likely to develop a more proinflammatory dietary pattern and consume less fiber and several vitamins, which may worsen the atopic outcome itself.

Major finding: The intake of fiber (P = .04), vitamin C (P = .02), vitamin E (P = .03), and vitamin B₇ (biotin) (P = .047) were significantly lower among children who developed vs did not develop AD in the first 10 years of life, with a significant association observed between presence of AD and a proinflammatory dietary pattern at 10 years of age (odds ratio 2.22; P = .02).

Study details: Findings are from the population-based LiNA cohort study including 211 10-year-old children.

Disclosures: This LiNA study was funded by the Department of Environmental Immunology, Helmholtz Centre for Environmental Research. JR Hebert declared owning controlling interest in Connecting Health Innovations LLC.

Source: Schütte O et al. Pro-inflammatory diet pictured in children with atopic dermatitis or food allergy: Nutritional data of the LiNA cohort. Front Nutr. 2022;9:868872 (Apr 8). Doi: 10.3389/fnut.2022.868872

Key clinical point: Antioxidants show favorable efficacy and safety as an adjunct therapy for atopic dermatitis (AD), particularly when supplemented with oral vitamin D and topical vitamin B₁₂.

Major finding: Overall, antioxidants vs placebo were associated with a significant reduction in disease severity scores (P < .0001), with a significant decrease in AD severity observed for oral supplementation with vitamin D (P = .01); combined vitamins D and E (P = .003); combined vitamins A, D, and E (P = .02); and topical vitamin B₁₂ (P < .0001). No serious adverse events were reported.

Study details: Findings are from a meta-analysis of 18 studies including 763 patients with AD.

Disclosures: This study did not receive any funding. No conflict of interests was reported.

Source: Yang H et al. Efficacy and safety profile of antioxidants in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials. Dermatol Ther. 2022 (May 3). Doi: 10.1111/dth.15549

Key clinical point: Antioxidants show favorable efficacy and safety as an adjunct therapy for atopic dermatitis (AD), particularly when supplemented with oral vitamin D and topical vitamin B₁₂.

Major finding: Overall, antioxidants vs placebo were associated with a significant reduction in disease severity scores (P < .0001), with a significant decrease in AD severity observed for oral supplementation with vitamin D (P = .01); combined vitamins D and E (P = .003); combined vitamins A, D, and E (P = .02); and topical vitamin B₁₂ (P < .0001). No serious adverse events were reported.

Study details: Findings are from a meta-analysis of 18 studies including 763 patients with AD.

Disclosures: This study did not receive any funding. No conflict of interests was reported.

Source: Yang H et al. Efficacy and safety profile of antioxidants in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials. Dermatol Ther. 2022 (May 3). Doi: 10.1111/dth.15549

Key clinical point: Antioxidants show favorable efficacy and safety as an adjunct therapy for atopic dermatitis (AD), particularly when supplemented with oral vitamin D and topical vitamin B₁₂.

Major finding: Overall, antioxidants vs placebo were associated with a significant reduction in disease severity scores (P < .0001), with a significant decrease in AD severity observed for oral supplementation with vitamin D (P = .01); combined vitamins D and E (P = .003); combined vitamins A, D, and E (P = .02); and topical vitamin B₁₂ (P < .0001). No serious adverse events were reported.

Study details: Findings are from a meta-analysis of 18 studies including 763 patients with AD.

Disclosures: This study did not receive any funding. No conflict of interests was reported.

Source: Yang H et al. Efficacy and safety profile of antioxidants in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials. Dermatol Ther. 2022 (May 3). Doi: 10.1111/dth.15549

Key clinical point: Dupilumab improved clinical scores in a real-world population of adolescents with moderate-to-severe atopic dermatitis (AD) and had a tolerable safety profile.

Major finding: After 16 weeks, the mean Eczema Area and Severity Index (EASI) score and Children Dermatology Life Quality Index and Numeric Rating Scale sleep loss scores reduced significantly by 79.8%, 72.9%, and 75.8%, respectively (all P < .01), with a higher proportion of patients with diffuse eczema vs. other clinical phenotypes reporting ≥90% and 100% improvement in EASI scores (P < .05). Adverse events (AE) were reported by 20.1% of adolescents, but none discontinued dupilumab because of AE.

Study details: This prospective study included 139 adolescents aged ≥12 to <18 years with moderate-to-severe AD who received dupilumab for 16 weeks.

Disclosures: This study did not receive any funding. Some authors declared serving as principal investigators, advisory board members, speakers, or consultants, or receiving personal fees, consulting fees, or payments or honoraria from several sources.

Source: Stingeni L et al. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience. J Eur Acad Dermatol Venereol. 2022 (Apr 12). Doi: 10.1111/jdv.18141

Key clinical point: Dupilumab improved clinical scores in a real-world population of adolescents with moderate-to-severe atopic dermatitis (AD) and had a tolerable safety profile.

Major finding: After 16 weeks, the mean Eczema Area and Severity Index (EASI) score and Children Dermatology Life Quality Index and Numeric Rating Scale sleep loss scores reduced significantly by 79.8%, 72.9%, and 75.8%, respectively (all P < .01), with a higher proportion of patients with diffuse eczema vs. other clinical phenotypes reporting ≥90% and 100% improvement in EASI scores (P < .05). Adverse events (AE) were reported by 20.1% of adolescents, but none discontinued dupilumab because of AE.

Study details: This prospective study included 139 adolescents aged ≥12 to <18 years with moderate-to-severe AD who received dupilumab for 16 weeks.

Disclosures: This study did not receive any funding. Some authors declared serving as principal investigators, advisory board members, speakers, or consultants, or receiving personal fees, consulting fees, or payments or honoraria from several sources.

Source: Stingeni L et al. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience. J Eur Acad Dermatol Venereol. 2022 (Apr 12). Doi: 10.1111/jdv.18141

Key clinical point: Dupilumab improved clinical scores in a real-world population of adolescents with moderate-to-severe atopic dermatitis (AD) and had a tolerable safety profile.

Major finding: After 16 weeks, the mean Eczema Area and Severity Index (EASI) score and Children Dermatology Life Quality Index and Numeric Rating Scale sleep loss scores reduced significantly by 79.8%, 72.9%, and 75.8%, respectively (all P < .01), with a higher proportion of patients with diffuse eczema vs. other clinical phenotypes reporting ≥90% and 100% improvement in EASI scores (P < .05). Adverse events (AE) were reported by 20.1% of adolescents, but none discontinued dupilumab because of AE.

Study details: This prospective study included 139 adolescents aged ≥12 to <18 years with moderate-to-severe AD who received dupilumab for 16 weeks.

Disclosures: This study did not receive any funding. Some authors declared serving as principal investigators, advisory board members, speakers, or consultants, or receiving personal fees, consulting fees, or payments or honoraria from several sources.

Source: Stingeni L et al. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience. J Eur Acad Dermatol Venereol. 2022 (Apr 12). Doi: 10.1111/jdv.18141

Key clinical point: Nemolizumab was safe and more effective than placebo in reducing the severity of atopic dermatitis (AD) or pruritus.

Major finding: Nemolizumab vs placebo significantly reduced the pruritus visual analogue scale score (weighted mean difference [WMD] −18.86; P < .001) and Eczema Area and Severity Index score (WMD −11.76; P = .009). Adverse events were mostly mild and similar in both the groups (P = .593).

Study details: This was a meta-analysis of 14 cohorts of participants from six randomized controlled studies that included 569 and 240 patients with AD or pruritus who received nemolizumab and placebo, respectively.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Liang J et al. Safety and efficacy of nemolizumab for atopic dermatitis with pruritus: a systematic review and meta-regression analysis of randomized controlled trials. Front Immunol. 2022;13:825312 (Apr 26). Doi: 10.3389/fimmu.2022.825312

Key clinical point: Nemolizumab was safe and more effective than placebo in reducing the severity of atopic dermatitis (AD) or pruritus.

Major finding: Nemolizumab vs placebo significantly reduced the pruritus visual analogue scale score (weighted mean difference [WMD] −18.86; P < .001) and Eczema Area and Severity Index score (WMD −11.76; P = .009). Adverse events were mostly mild and similar in both the groups (P = .593).

Study details: This was a meta-analysis of 14 cohorts of participants from six randomized controlled studies that included 569 and 240 patients with AD or pruritus who received nemolizumab and placebo, respectively.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Liang J et al. Safety and efficacy of nemolizumab for atopic dermatitis with pruritus: a systematic review and meta-regression analysis of randomized controlled trials. Front Immunol. 2022;13:825312 (Apr 26). Doi: 10.3389/fimmu.2022.825312

Key clinical point: Nemolizumab was safe and more effective than placebo in reducing the severity of atopic dermatitis (AD) or pruritus.

Major finding: Nemolizumab vs placebo significantly reduced the pruritus visual analogue scale score (weighted mean difference [WMD] −18.86; P < .001) and Eczema Area and Severity Index score (WMD −11.76; P = .009). Adverse events were mostly mild and similar in both the groups (P = .593).

Study details: This was a meta-analysis of 14 cohorts of participants from six randomized controlled studies that included 569 and 240 patients with AD or pruritus who received nemolizumab and placebo, respectively.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Liang J et al. Safety and efficacy of nemolizumab for atopic dermatitis with pruritus: a systematic review and meta-regression analysis of randomized controlled trials. Front Immunol. 2022;13:825312 (Apr 26). Doi: 10.3389/fimmu.2022.825312

Key clinical point: Children with atopic dermatitis (AD) may have a higher sensitivity to contact allergens, such as fragrances and metals, than children without AD.

Major finding: Overall, 36.9% vs 26.4% of children with vs without AD presented with at least one positive patch test. Children with v. without AD showed a higher prevalence of ≥1 positive patch test for allergens, such as nickel sulfate, cobalt chloride, methylisothiazolinone, fragrance mix-2, potassium dichromate, fragrance mix-1, methylchloroisothiazolinone/methylisothiazolinone, and neomycin sulfate, with the prevalence difference being highest for fragrance mix-1 (5.8% vs 0.9%; P = .004293).

Study details: This retrospective study included 432 children aged 0-14 years with eczematous dermatitis who underwent patch testing, of which 23.8% of children were diagnosed with AD.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Bonamonte D et al. Contact allergy in children with and without atopic dermatitis: An Italian multicentre study. Contact Dermatitis. 2022 (Apr 21). Doi: 10.1111/cod.14130

Key clinical point: Children with atopic dermatitis (AD) may have a higher sensitivity to contact allergens, such as fragrances and metals, than children without AD.

Major finding: Overall, 36.9% vs 26.4% of children with vs without AD presented with at least one positive patch test. Children with v. without AD showed a higher prevalence of ≥1 positive patch test for allergens, such as nickel sulfate, cobalt chloride, methylisothiazolinone, fragrance mix-2, potassium dichromate, fragrance mix-1, methylchloroisothiazolinone/methylisothiazolinone, and neomycin sulfate, with the prevalence difference being highest for fragrance mix-1 (5.8% vs 0.9%; P = .004293).

Study details: This retrospective study included 432 children aged 0-14 years with eczematous dermatitis who underwent patch testing, of which 23.8% of children were diagnosed with AD.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Bonamonte D et al. Contact allergy in children with and without atopic dermatitis: An Italian multicentre study. Contact Dermatitis. 2022 (Apr 21). Doi: 10.1111/cod.14130

Key clinical point: Children with atopic dermatitis (AD) may have a higher sensitivity to contact allergens, such as fragrances and metals, than children without AD.

Major finding: Overall, 36.9% vs 26.4% of children with vs without AD presented with at least one positive patch test. Children with v. without AD showed a higher prevalence of ≥1 positive patch test for allergens, such as nickel sulfate, cobalt chloride, methylisothiazolinone, fragrance mix-2, potassium dichromate, fragrance mix-1, methylchloroisothiazolinone/methylisothiazolinone, and neomycin sulfate, with the prevalence difference being highest for fragrance mix-1 (5.8% vs 0.9%; P = .004293).

Study details: This retrospective study included 432 children aged 0-14 years with eczematous dermatitis who underwent patch testing, of which 23.8% of children were diagnosed with AD.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Bonamonte D et al. Contact allergy in children with and without atopic dermatitis: An Italian multicentre study. Contact Dermatitis. 2022 (Apr 21). Doi: 10.1111/cod.14130

Key clinical point: Dupilumab showed an acceptable safety profile and sustained efficacy through 4 years in adults with moderate-to-severe atopic dermatitis (AD).

Major finding: At 4 years, the exposure-adjusted incidence rate of treatment emergent adverse events (TEAE) was 256.86 events/100 patient-years, with most events being mild to moderate in severity. At least one serious and severe TEAE was experienced by 10.4% and 9.8% of patients in two dose categories. At week 204, the mean Eczema Area and Severity Index (EASI) score improved by 91.07%, with patients switching from 300 mg dupilumab weekly to every-2-weeks dosing while maintaining EASI scores up to 48 weeks post-transition.

Study details: Findings are from an interim analysis of the ongoing phase 3, LIBERTY AD open-label extension study including 2677 adults with moderate-to-severe AD who received 300 mg dupilumab  weekly or every 2 weeks in previous phase 1-3 AD trials.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Seven authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi, and other authors reported ties with various sources.

Source: Beck LA et al. Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2022 (May 3). Doi: 10.1007/s40257-022-00685-0

Key clinical point: Dupilumab showed an acceptable safety profile and sustained efficacy through 4 years in adults with moderate-to-severe atopic dermatitis (AD).

Major finding: At 4 years, the exposure-adjusted incidence rate of treatment emergent adverse events (TEAE) was 256.86 events/100 patient-years, with most events being mild to moderate in severity. At least one serious and severe TEAE was experienced by 10.4% and 9.8% of patients in two dose categories. At week 204, the mean Eczema Area and Severity Index (EASI) score improved by 91.07%, with patients switching from 300 mg dupilumab weekly to every-2-weeks dosing while maintaining EASI scores up to 48 weeks post-transition.

Study details: Findings are from an interim analysis of the ongoing phase 3, LIBERTY AD open-label extension study including 2677 adults with moderate-to-severe AD who received 300 mg dupilumab  weekly or every 2 weeks in previous phase 1-3 AD trials.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Seven authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi, and other authors reported ties with various sources.

Source: Beck LA et al. Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2022 (May 3). Doi: 10.1007/s40257-022-00685-0

Key clinical point: Dupilumab showed an acceptable safety profile and sustained efficacy through 4 years in adults with moderate-to-severe atopic dermatitis (AD).

Major finding: At 4 years, the exposure-adjusted incidence rate of treatment emergent adverse events (TEAE) was 256.86 events/100 patient-years, with most events being mild to moderate in severity. At least one serious and severe TEAE was experienced by 10.4% and 9.8% of patients in two dose categories. At week 204, the mean Eczema Area and Severity Index (EASI) score improved by 91.07%, with patients switching from 300 mg dupilumab weekly to every-2-weeks dosing while maintaining EASI scores up to 48 weeks post-transition.

Study details: Findings are from an interim analysis of the ongoing phase 3, LIBERTY AD open-label extension study including 2677 adults with moderate-to-severe AD who received 300 mg dupilumab  weekly or every 2 weeks in previous phase 1-3 AD trials.

Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Seven authors declared being employees or shareholders of Regeneron Pharmaceuticals or Sanofi, and other authors reported ties with various sources.

Source: Beck LA et al. Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2022 (May 3). Doi: 10.1007/s40257-022-00685-0

Key clinical point: Baricitinib plus topical corticosteroids (TCS) improved the signs and symptoms of atopic dermatitis (AD) through 1 year along with a consistent safety profile in patients with moderate-to-severe AD and an inadequate response, intolerance, or contraindication to cyclosporine A (CyA).

Major finding: At week 16, ≥75% improvement in the Eczema Area and Severity Index was achieved by a significantly higher proportion of patients receiving 4 mg baricitinib+TCS vs placebo+TCS (32% vs 17%; P = .031), with improvements maintained through week 52. Treatment emergent adverse events were more frequent with baricitinib, but were mostly mild or moderate in severity.

Study details: Findings are from the phase 3 BREEZE-AD4 study including 463 patients with moderate-to-severe AD and an inadequate response, contraindication, or intolerance to CyA who were randomly assigned to receive placebo+TCS or 1, 2, or 4 mg baricitinib+TCS for 52 weeks.

Disclosures: Eli Lilly and Company developed baricitinib. Six authors declared being employees and shareholders of Eli Lilly, and other authors reported ties with various sources, including Eli Lilly.

Source: Bieber T et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance, or contraindication to cyclosporine: Results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol. 2022 (Apr 28). Doi: 10.1111/bjd.21630

Key clinical point: Baricitinib plus topical corticosteroids (TCS) improved the signs and symptoms of atopic dermatitis (AD) through 1 year along with a consistent safety profile in patients with moderate-to-severe AD and an inadequate response, intolerance, or contraindication to cyclosporine A (CyA).

Major finding: At week 16, ≥75% improvement in the Eczema Area and Severity Index was achieved by a significantly higher proportion of patients receiving 4 mg baricitinib+TCS vs placebo+TCS (32% vs 17%; P = .031), with improvements maintained through week 52. Treatment emergent adverse events were more frequent with baricitinib, but were mostly mild or moderate in severity.

Study details: Findings are from the phase 3 BREEZE-AD4 study including 463 patients with moderate-to-severe AD and an inadequate response, contraindication, or intolerance to CyA who were randomly assigned to receive placebo+TCS or 1, 2, or 4 mg baricitinib+TCS for 52 weeks.

Disclosures: Eli Lilly and Company developed baricitinib. Six authors declared being employees and shareholders of Eli Lilly, and other authors reported ties with various sources, including Eli Lilly.

Source: Bieber T et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance, or contraindication to cyclosporine: Results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol. 2022 (Apr 28). Doi: 10.1111/bjd.21630

Key clinical point: Baricitinib plus topical corticosteroids (TCS) improved the signs and symptoms of atopic dermatitis (AD) through 1 year along with a consistent safety profile in patients with moderate-to-severe AD and an inadequate response, intolerance, or contraindication to cyclosporine A (CyA).

Major finding: At week 16, ≥75% improvement in the Eczema Area and Severity Index was achieved by a significantly higher proportion of patients receiving 4 mg baricitinib+TCS vs placebo+TCS (32% vs 17%; P = .031), with improvements maintained through week 52. Treatment emergent adverse events were more frequent with baricitinib, but were mostly mild or moderate in severity.

Study details: Findings are from the phase 3 BREEZE-AD4 study including 463 patients with moderate-to-severe AD and an inadequate response, contraindication, or intolerance to CyA who were randomly assigned to receive placebo+TCS or 1, 2, or 4 mg baricitinib+TCS for 52 weeks.

Disclosures: Eli Lilly and Company developed baricitinib. Six authors declared being employees and shareholders of Eli Lilly, and other authors reported ties with various sources, including Eli Lilly.

Source: Bieber T et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance, or contraindication to cyclosporine: Results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol. 2022 (Apr 28). Doi: 10.1111/bjd.21630