Atopic Dermatitis

Key clinical point: Pharmacological interventions aimed at reducing disease severity in patients with moderate to severe atopic dermatitis (AD) are also effective for improving anxiety and depression.

Major finding: Pharmacologic interventions for AD led to significant improvements in anxiety levels (standardized mean difference [SMD] −0.29; 95% CI −0.49 to −0.09) and depression severity (SMD −0.27; 95% CI −0.45 to −0.08) and an overall significant improvement in Hospital Anxiety and Depression scale scores (SMD −0.50; 95% CI −0.064 to −0.35).

Study details: This meta-analysis of seven phase 2b or 3 randomized controlled trials included 4723 patients with AD who were treated with either abrocitinib, baricitinib, dupilumab, tralokinumab, or placebo.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Hartono SP, Chatrath S, Aktas ON, et al. Interventions for anxiety and depression in patients with atopic dermatitis: A systematic review and meta-analysis. Sci Rep. 2024;14:8844 (Apr 17). Source

Key clinical point: Pharmacological interventions aimed at reducing disease severity in patients with moderate to severe atopic dermatitis (AD) are also effective for improving anxiety and depression.

Major finding: Pharmacologic interventions for AD led to significant improvements in anxiety levels (standardized mean difference [SMD] −0.29; 95% CI −0.49 to −0.09) and depression severity (SMD −0.27; 95% CI −0.45 to −0.08) and an overall significant improvement in Hospital Anxiety and Depression scale scores (SMD −0.50; 95% CI −0.064 to −0.35).

Study details: This meta-analysis of seven phase 2b or 3 randomized controlled trials included 4723 patients with AD who were treated with either abrocitinib, baricitinib, dupilumab, tralokinumab, or placebo.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Hartono SP, Chatrath S, Aktas ON, et al. Interventions for anxiety and depression in patients with atopic dermatitis: A systematic review and meta-analysis. Sci Rep. 2024;14:8844 (Apr 17). Source

Key clinical point: Pharmacological interventions aimed at reducing disease severity in patients with moderate to severe atopic dermatitis (AD) are also effective for improving anxiety and depression.

Major finding: Pharmacologic interventions for AD led to significant improvements in anxiety levels (standardized mean difference [SMD] −0.29; 95% CI −0.49 to −0.09) and depression severity (SMD −0.27; 95% CI −0.45 to −0.08) and an overall significant improvement in Hospital Anxiety and Depression scale scores (SMD −0.50; 95% CI −0.064 to −0.35).

Study details: This meta-analysis of seven phase 2b or 3 randomized controlled trials included 4723 patients with AD who were treated with either abrocitinib, baricitinib, dupilumab, tralokinumab, or placebo.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Hartono SP, Chatrath S, Aktas ON, et al. Interventions for anxiety and depression in patients with atopic dermatitis: A systematic review and meta-analysis. Sci Rep. 2024;14:8844 (Apr 17). Source

Key clinical point: When combined with topical corticosteroids (TCS), tralokinumab and dupilumab demonstrate similar efficacy in the treatment of patients with moderate to severe atopic dermatitis (AD) at 32 weeks of therapy.

Major finding: At week 32, tralokinumab and dupilumab treatment, both in combination with TCS, led to a similar proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 (49.9% vs 39.3%; P = .95) or 75% improvement in the Eczema Area Severity Index scores (71.5% vs 71.9%; P = .95).

Study details: This unanchored matching-adjusted indirect comparison study analyzed the individual patient data of adults with moderate to severe AD (sample size 123.4) treated with tralokinumab plus TCS in ECZTRA 3, which were matched with the aggregate data of 106 patients treated with dupilumab plus TCS in the LIBERTY AD CHRONOS trial.

Disclosures: This study was funded by LEO Pharma. Four authors declared being employees of LEO Pharma. The other authors declared receiving consultancy or speaker honoraria from or having other ties with various sources, including LEO Pharma.

Source: Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14:983-992 (Apr 13). doi: 10.1007/s13555-024-01143-x Source

Key clinical point: When combined with topical corticosteroids (TCS), tralokinumab and dupilumab demonstrate similar efficacy in the treatment of patients with moderate to severe atopic dermatitis (AD) at 32 weeks of therapy.

Major finding: At week 32, tralokinumab and dupilumab treatment, both in combination with TCS, led to a similar proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 (49.9% vs 39.3%; P = .95) or 75% improvement in the Eczema Area Severity Index scores (71.5% vs 71.9%; P = .95).

Study details: This unanchored matching-adjusted indirect comparison study analyzed the individual patient data of adults with moderate to severe AD (sample size 123.4) treated with tralokinumab plus TCS in ECZTRA 3, which were matched with the aggregate data of 106 patients treated with dupilumab plus TCS in the LIBERTY AD CHRONOS trial.

Disclosures: This study was funded by LEO Pharma. Four authors declared being employees of LEO Pharma. The other authors declared receiving consultancy or speaker honoraria from or having other ties with various sources, including LEO Pharma.

Source: Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14:983-992 (Apr 13). doi: 10.1007/s13555-024-01143-x Source

Key clinical point: When combined with topical corticosteroids (TCS), tralokinumab and dupilumab demonstrate similar efficacy in the treatment of patients with moderate to severe atopic dermatitis (AD) at 32 weeks of therapy.

Major finding: At week 32, tralokinumab and dupilumab treatment, both in combination with TCS, led to a similar proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 (49.9% vs 39.3%; P = .95) or 75% improvement in the Eczema Area Severity Index scores (71.5% vs 71.9%; P = .95).

Study details: This unanchored matching-adjusted indirect comparison study analyzed the individual patient data of adults with moderate to severe AD (sample size 123.4) treated with tralokinumab plus TCS in ECZTRA 3, which were matched with the aggregate data of 106 patients treated with dupilumab plus TCS in the LIBERTY AD CHRONOS trial.

Disclosures: This study was funded by LEO Pharma. Four authors declared being employees of LEO Pharma. The other authors declared receiving consultancy or speaker honoraria from or having other ties with various sources, including LEO Pharma.

Source: Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14:983-992 (Apr 13). doi: 10.1007/s13555-024-01143-x Source

Key clinical point: Topical 1.5% ruxolitinib was effective and well-tolerated and offered long-term disease control with as-needed use in adolescents with atopic dermatitis (AD).

Major finding: At week 8, a substantially higher number of patients receiving 1.5% ruxolitinib vs vehicle achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2 grade improvement from baseline (50.6% vs 14.0%) and ≥75% improvement in the Eczema Area and Severity Index score (60.9% vs 34.9%), with sustained or increased proportion of patients achieving an IGA score of 0 or 1 during the long-term safety (LTS) period. No serious adverse events were reported.

Study details: This study used pooled data from two phase 3 trials (TRuE-AD1 and TRuE-AD2) and included 137 adolescents (age, 12-17 years) with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, followed by an LTS period lasting up to 52 weeks.

Disclosures: This study was funded by Incyte Corporation. Four authors declared being employees or shareholders of Incyte Corporation. Several authors declared ties with various sources, including Incyte Corporation.

Source: Eichenfield LF, Simpson EL, Papp K, et al. Efficacy, safety, and long-term disease control of ruxolitinib cream among adolescents with atopic dermatitis: Pooled results from two randomized phase 3 studies. Am J Clin Dermatol. 2024 (May 2). doi:  10.1007/s40257-024-00855-2 Source

Key clinical point: Topical 1.5% ruxolitinib was effective and well-tolerated and offered long-term disease control with as-needed use in adolescents with atopic dermatitis (AD).

Major finding: At week 8, a substantially higher number of patients receiving 1.5% ruxolitinib vs vehicle achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2 grade improvement from baseline (50.6% vs 14.0%) and ≥75% improvement in the Eczema Area and Severity Index score (60.9% vs 34.9%), with sustained or increased proportion of patients achieving an IGA score of 0 or 1 during the long-term safety (LTS) period. No serious adverse events were reported.

Study details: This study used pooled data from two phase 3 trials (TRuE-AD1 and TRuE-AD2) and included 137 adolescents (age, 12-17 years) with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, followed by an LTS period lasting up to 52 weeks.

Disclosures: This study was funded by Incyte Corporation. Four authors declared being employees or shareholders of Incyte Corporation. Several authors declared ties with various sources, including Incyte Corporation.

Source: Eichenfield LF, Simpson EL, Papp K, et al. Efficacy, safety, and long-term disease control of ruxolitinib cream among adolescents with atopic dermatitis: Pooled results from two randomized phase 3 studies. Am J Clin Dermatol. 2024 (May 2). doi:  10.1007/s40257-024-00855-2 Source

Key clinical point: Topical 1.5% ruxolitinib was effective and well-tolerated and offered long-term disease control with as-needed use in adolescents with atopic dermatitis (AD).

Major finding: At week 8, a substantially higher number of patients receiving 1.5% ruxolitinib vs vehicle achieved an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2 grade improvement from baseline (50.6% vs 14.0%) and ≥75% improvement in the Eczema Area and Severity Index score (60.9% vs 34.9%), with sustained or increased proportion of patients achieving an IGA score of 0 or 1 during the long-term safety (LTS) period. No serious adverse events were reported.

Study details: This study used pooled data from two phase 3 trials (TRuE-AD1 and TRuE-AD2) and included 137 adolescents (age, 12-17 years) with AD who were randomly assigned to receive 0.75% or 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, followed by an LTS period lasting up to 52 weeks.

Disclosures: This study was funded by Incyte Corporation. Four authors declared being employees or shareholders of Incyte Corporation. Several authors declared ties with various sources, including Incyte Corporation.

Source: Eichenfield LF, Simpson EL, Papp K, et al. Efficacy, safety, and long-term disease control of ruxolitinib cream among adolescents with atopic dermatitis: Pooled results from two randomized phase 3 studies. Am J Clin Dermatol. 2024 (May 2). doi:  10.1007/s40257-024-00855-2 Source

Key clinical point: Obesity is significantly associated with patient- and physician-assessed measures of atopic dermatitis (AD) disease severity.

Major finding: Increased body mass index (BMI) values were associated with higher disease severity as assessed by objective Scoring AD (adjusted β 1.24; P = .013) and patient-oriented eczema measure (adjusted β 1.09; P = .038) scores.

Study details: This study based on data from the prospective observational TREATgermany registry included 1416 patients with moderate to severe AD who were either underweight (BMI < 18.5 kg/m²; n = 33), normal weight or overweight (nonobese; BMI ≥ 18.5 and < 30 kg/m²; n = 1149), or obese (BMI ≥ 30 kg/m²; n = 234).

Disclosures: The TREATgermany registry is supported by AbbVie Deutschland GmbH & Co. KG, Galderma SA, LEO Pharma GmbH, Lilly Deutschland GmbH, Pfizer Inc., and Sanofi. Eight authors declared serving as consultants or lecturers for or receiving research grants, personal fees, or lecture or consulting honoraria from various sources, including some of the supporters of TREATgermany.

Source: Traidl S, Hollstein MM, Kroeger N, et al, and The TREATgermany Study Group. Obesity is linked to disease severity in moderate to severe atopic dermatitis—Data from the prospective observational TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Apr 25). doi:  10.1111/jdv.20042 Source

Key clinical point: Obesity is significantly associated with patient- and physician-assessed measures of atopic dermatitis (AD) disease severity.

Major finding: Increased body mass index (BMI) values were associated with higher disease severity as assessed by objective Scoring AD (adjusted β 1.24; P = .013) and patient-oriented eczema measure (adjusted β 1.09; P = .038) scores.

Study details: This study based on data from the prospective observational TREATgermany registry included 1416 patients with moderate to severe AD who were either underweight (BMI < 18.5 kg/m²; n = 33), normal weight or overweight (nonobese; BMI ≥ 18.5 and < 30 kg/m²; n = 1149), or obese (BMI ≥ 30 kg/m²; n = 234).

Disclosures: The TREATgermany registry is supported by AbbVie Deutschland GmbH & Co. KG, Galderma SA, LEO Pharma GmbH, Lilly Deutschland GmbH, Pfizer Inc., and Sanofi. Eight authors declared serving as consultants or lecturers for or receiving research grants, personal fees, or lecture or consulting honoraria from various sources, including some of the supporters of TREATgermany.

Source: Traidl S, Hollstein MM, Kroeger N, et al, and The TREATgermany Study Group. Obesity is linked to disease severity in moderate to severe atopic dermatitis—Data from the prospective observational TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Apr 25). doi:  10.1111/jdv.20042 Source

Key clinical point: Obesity is significantly associated with patient- and physician-assessed measures of atopic dermatitis (AD) disease severity.

Major finding: Increased body mass index (BMI) values were associated with higher disease severity as assessed by objective Scoring AD (adjusted β 1.24; P = .013) and patient-oriented eczema measure (adjusted β 1.09; P = .038) scores.

Study details: This study based on data from the prospective observational TREATgermany registry included 1416 patients with moderate to severe AD who were either underweight (BMI < 18.5 kg/m²; n = 33), normal weight or overweight (nonobese; BMI ≥ 18.5 and < 30 kg/m²; n = 1149), or obese (BMI ≥ 30 kg/m²; n = 234).

Disclosures: The TREATgermany registry is supported by AbbVie Deutschland GmbH & Co. KG, Galderma SA, LEO Pharma GmbH, Lilly Deutschland GmbH, Pfizer Inc., and Sanofi. Eight authors declared serving as consultants or lecturers for or receiving research grants, personal fees, or lecture or consulting honoraria from various sources, including some of the supporters of TREATgermany.

Source: Traidl S, Hollstein MM, Kroeger N, et al, and The TREATgermany Study Group. Obesity is linked to disease severity in moderate to severe atopic dermatitis—Data from the prospective observational TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Apr 25). doi:  10.1111/jdv.20042 Source

Key clinical point: Antibiotic use early in life, especially within one year of age, disrupts the gut microbiome and increases the risk for atopic dermatitis (AD) at 5 years of age.

Major finding: Children who received antibiotics during the first year of life vs later were significantly more likely to develop AD at 5 years of age (adjusted odds ratio [aOR] 1.81; P < .001), with an increased number of antibiotic courses leading to a dose-response-like increased risk for AD (1 course: aOR 1.67; P = .0044; ≥ 2 courses: aOR 2.16; P = .0030).

Study details: This study analyzed the clinical data for AD diagnosis at age 5 years of 2484 children from the prospective, general population CHILD birth cohort, which enrolled pregnant women and infants with no congenital abnormalities born at ≥ 34 weeks of gestation.

Disclosures: The CHILD Study is funded by the Canadian Institutes of Health Research, the Allergy, Genes, and Environment Network of Centres of Excellence, Debbie and Don Morrison, and others. The authors declared no conflicts of interest.

Source: Hoskinson C, Medeleanu MV, Reyna ME, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 (Apr 24). doi: 10.1016/j.jaci.2024.03.025 Source

Key clinical point: Antibiotic use early in life, especially within one year of age, disrupts the gut microbiome and increases the risk for atopic dermatitis (AD) at 5 years of age.

Major finding: Children who received antibiotics during the first year of life vs later were significantly more likely to develop AD at 5 years of age (adjusted odds ratio [aOR] 1.81; P < .001), with an increased number of antibiotic courses leading to a dose-response-like increased risk for AD (1 course: aOR 1.67; P = .0044; ≥ 2 courses: aOR 2.16; P = .0030).

Study details: This study analyzed the clinical data for AD diagnosis at age 5 years of 2484 children from the prospective, general population CHILD birth cohort, which enrolled pregnant women and infants with no congenital abnormalities born at ≥ 34 weeks of gestation.

Disclosures: The CHILD Study is funded by the Canadian Institutes of Health Research, the Allergy, Genes, and Environment Network of Centres of Excellence, Debbie and Don Morrison, and others. The authors declared no conflicts of interest.

Source: Hoskinson C, Medeleanu MV, Reyna ME, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 (Apr 24). doi: 10.1016/j.jaci.2024.03.025 Source

Key clinical point: Antibiotic use early in life, especially within one year of age, disrupts the gut microbiome and increases the risk for atopic dermatitis (AD) at 5 years of age.

Major finding: Children who received antibiotics during the first year of life vs later were significantly more likely to develop AD at 5 years of age (adjusted odds ratio [aOR] 1.81; P < .001), with an increased number of antibiotic courses leading to a dose-response-like increased risk for AD (1 course: aOR 1.67; P = .0044; ≥ 2 courses: aOR 2.16; P = .0030).

Study details: This study analyzed the clinical data for AD diagnosis at age 5 years of 2484 children from the prospective, general population CHILD birth cohort, which enrolled pregnant women and infants with no congenital abnormalities born at ≥ 34 weeks of gestation.

Disclosures: The CHILD Study is funded by the Canadian Institutes of Health Research, the Allergy, Genes, and Environment Network of Centres of Excellence, Debbie and Don Morrison, and others. The authors declared no conflicts of interest.

Source: Hoskinson C, Medeleanu MV, Reyna ME, et al. Antibiotics within first year are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 (Apr 24). doi: 10.1016/j.jaci.2024.03.025 Source

In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."

Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.

Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.

Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much. 

Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better. 

In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
 

In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."

Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.

Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.

Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much. 

Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better. 

In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
 

In "Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study," Lerchova and colleagues found a statistically significant increased risk for inflammatory bowel disease (IBD) in children with atopic dermatitis. The study had a large patient population, giving it the power to identify very small differences. The researchers found increased risks for IBD, Crohn's disease, and ulcerative colitis (UC) in children with atopic dermatitis; UC had the greatest relative risk. But I don't think this risk was clinically meaningful. About 2 in every 1000 children with atopic dermatitis had UC, whereas about 1 in every 1000 children without atopic dermatitis had UC. Even if the increased absolute risk of 1 in 1000 children was due to atopic dermatitis and not to other factors, I don't think it justifies the authors' conclusion that "these findings might be useful in identifying at-risk individuals for IBD."

Sometimes reviewing articles makes me feel like a crotchety old man. A study by Guttman-Yassky and colleagues, "Targeting IL-13 With Tralokinumab Normalizes Type 2 Inflammation in Atopic Dermatitis Both Early and at 2 Years," didn't seem to test any specific hypothesis. The researchers just looked at a variety of inflammation markers in patients with atopic dermatitis treated with tralokinumab, an interleukin-13 (IL-13) antagonist. In these patients, as expected, the atopic dermatitis improved; so did the inflammatory markers. Did we learn anything clinically useful? I don't think so. We already know that IL-13 is important in atopic dermatitis because when we block IL-13, atopic dermatitis improves.

Vitamin D supplementation doesn't appear to improve atopic dermatitis, as reported by Borzutzky and colleagues in "Effect of Weekly Vitamin D Supplementation on the Severity of Atopic Dermatitis and Type 2 Immunity Biomarkers in Children: A Randomized Controlled Trial." A group of 101 children with atopic dermatitis were randomly assigned to receive oral vitamin D supplementation or placebo. The two groups improved to a similar extent. If you know me, you know I'm wondering whether they took the medication. It appears that they did, because at baseline most of the children were vitamin D deficient, and vitamin D levels improved greatly in the group treated with vitamin D but not in the placebo group.

Journals such as the Journal of the American Academy of Dermatology should require articles to report absolute risk. In "Risk of Lymphoma in Patients With Atopic Dermatitis: A Case-Control Study in the All of Us Database," Powers and colleagues tell us that atopic dermatitis is associated with a statistically significantly increased risk for lymphoma. This means that increased risk wasn't likely due to chance alone. The article says nothing, as far as I could tell, about how big the risk is. Does everyone get lymphoma? Or is it a one in a million risk? Without knowing the absolute risk, the relative risk doesn't tell us whether there is a clinically meaningful increased risk or not. I suspect the increased risk is small. If the incidence of lymphoma is about 2 in 10,000 and peripheral T-cell lymphomas (PTCL) account for 10% of those, even a fourfold increase in the risk for PTCL (the form of lymphoma with the highest relative risk) would not amount to much. 

Traidl and colleagues report in "Treatment of Moderate-to-Severe Atopic Dermatitis With Baricitinib: Results From an Interim Analysis of the TREATgermany Registry" that the Janus kinase inhibitor baricitinib makes atopic dermatitis better. 

In "Dupilumab Therapy for Atopic Dermatitis Is Associated With Increased Risk of Cutaneous T Cell Lymphoma," Hasan and colleagues report that "it requires 738 prescriptions of dupilumab to produce one case of CTCL [cutaneous T-cell lymphoma]." It seems that this finding could easily be due to 1 in 738 people with a rash thought to be severe atopic dermatitis needing dupilumab having CTCL, not atopic dermatitis, to begin with. If we were to wonder whether dupilumab causes CTCL, perhaps it would be better to study asthma patients treated with or without dupilumab.
 

Key clinical point: Specific behavioral patterns of attention-deficit/hyperactivity disorder, such as impulsivity and hyperactivity, were associated with the development of prurigo nodularis (PN) in children with atopic dermatitis (AD), regardless of AD severity.

Major finding: Among children with AD, the impulsivity/hyperactivity score was significantly higher in those with vs without PN (5.5 ± 4.2 vs 2.9 ± 2.9; P = .038); no significant differences were observed in Eczema Area Severity Index scores, itch numeric rating scale scores, or other AD outcomes in children with vs without PN (P > .05).

Study details: This cross-sectional study included 39 children with AD who did (n = 21) or did not (n = 18) have PN.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kim Y, Lee J, Shin K, et al. Association between prurigo nodularis and behavioural patterns of attention-deficit/hyperactivity disorder in children with atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2024(Mar 27). doi: 10.1111/jdv.19967  Source

Key clinical point: Specific behavioral patterns of attention-deficit/hyperactivity disorder, such as impulsivity and hyperactivity, were associated with the development of prurigo nodularis (PN) in children with atopic dermatitis (AD), regardless of AD severity.

Major finding: Among children with AD, the impulsivity/hyperactivity score was significantly higher in those with vs without PN (5.5 ± 4.2 vs 2.9 ± 2.9; P = .038); no significant differences were observed in Eczema Area Severity Index scores, itch numeric rating scale scores, or other AD outcomes in children with vs without PN (P > .05).

Study details: This cross-sectional study included 39 children with AD who did (n = 21) or did not (n = 18) have PN.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kim Y, Lee J, Shin K, et al. Association between prurigo nodularis and behavioural patterns of attention-deficit/hyperactivity disorder in children with atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2024(Mar 27). doi: 10.1111/jdv.19967  Source

Key clinical point: Specific behavioral patterns of attention-deficit/hyperactivity disorder, such as impulsivity and hyperactivity, were associated with the development of prurigo nodularis (PN) in children with atopic dermatitis (AD), regardless of AD severity.

Major finding: Among children with AD, the impulsivity/hyperactivity score was significantly higher in those with vs without PN (5.5 ± 4.2 vs 2.9 ± 2.9; P = .038); no significant differences were observed in Eczema Area Severity Index scores, itch numeric rating scale scores, or other AD outcomes in children with vs without PN (P > .05).

Study details: This cross-sectional study included 39 children with AD who did (n = 21) or did not (n = 18) have PN.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kim Y, Lee J, Shin K, et al. Association between prurigo nodularis and behavioural patterns of attention-deficit/hyperactivity disorder in children with atopic dermatitis: A cross-sectional study. J Eur Acad Dermatol Venereol. 2024(Mar 27). doi: 10.1111/jdv.19967  Source

Key clinical point: Upadacitinib treatment rapidly and sustainably improved multiple patient-reported outcomes, including itch, in adults and adolescents with moderate to severe atopic dermatitis (AD).

Major finding: At week 1, more than 10% and 15% of patients receiving 15 and 30 mg upadacitinib, respectively, experienced improvements in itch; thereafter, response rates increased steadily and sustainably through week 52. Similar improvements were observed for pain and other skin symptoms.

Study details: This pooled analysis included 1609 adults and adolescents with moderate to severe AD from the phase 3 Measure Up 1 and Measure Up 2 studies who had received upadacitinib (15 mg n = 557; 30 mg n = 567) or placebo (followed by upadacitinib 15 or 30 mg after 16 weeks; n = 485).

Disclosures: This study was funded by AbbVie, Inc. Eight authors declared being employees of or holding stock or stock options in AbbVie. The other authors declared serving as speakers for, receiving consulting fees, or having other ties with various sources, including AbbVie.

Source: Silverberg JI, Gooderham MJ, Paller AS, et al. Early and sustained improvements in symptoms and quality of life with upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: 52-week results from two phase III randomized clinical trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024 (Mar 25). doi: 10.1007/s40257-024-00853-4 Source

Key clinical point: Upadacitinib treatment rapidly and sustainably improved multiple patient-reported outcomes, including itch, in adults and adolescents with moderate to severe atopic dermatitis (AD).

Major finding: At week 1, more than 10% and 15% of patients receiving 15 and 30 mg upadacitinib, respectively, experienced improvements in itch; thereafter, response rates increased steadily and sustainably through week 52. Similar improvements were observed for pain and other skin symptoms.

Study details: This pooled analysis included 1609 adults and adolescents with moderate to severe AD from the phase 3 Measure Up 1 and Measure Up 2 studies who had received upadacitinib (15 mg n = 557; 30 mg n = 567) or placebo (followed by upadacitinib 15 or 30 mg after 16 weeks; n = 485).

Disclosures: This study was funded by AbbVie, Inc. Eight authors declared being employees of or holding stock or stock options in AbbVie. The other authors declared serving as speakers for, receiving consulting fees, or having other ties with various sources, including AbbVie.

Source: Silverberg JI, Gooderham MJ, Paller AS, et al. Early and sustained improvements in symptoms and quality of life with upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: 52-week results from two phase III randomized clinical trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024 (Mar 25). doi: 10.1007/s40257-024-00853-4 Source

Key clinical point: Upadacitinib treatment rapidly and sustainably improved multiple patient-reported outcomes, including itch, in adults and adolescents with moderate to severe atopic dermatitis (AD).

Major finding: At week 1, more than 10% and 15% of patients receiving 15 and 30 mg upadacitinib, respectively, experienced improvements in itch; thereafter, response rates increased steadily and sustainably through week 52. Similar improvements were observed for pain and other skin symptoms.

Study details: This pooled analysis included 1609 adults and adolescents with moderate to severe AD from the phase 3 Measure Up 1 and Measure Up 2 studies who had received upadacitinib (15 mg n = 557; 30 mg n = 567) or placebo (followed by upadacitinib 15 or 30 mg after 16 weeks; n = 485).

Disclosures: This study was funded by AbbVie, Inc. Eight authors declared being employees of or holding stock or stock options in AbbVie. The other authors declared serving as speakers for, receiving consulting fees, or having other ties with various sources, including AbbVie.

Source: Silverberg JI, Gooderham MJ, Paller AS, et al. Early and sustained improvements in symptoms and quality of life with upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: 52-week results from two phase III randomized clinical trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024 (Mar 25). doi: 10.1007/s40257-024-00853-4 Source

Key clinical point: Patients with atopic dermatitis (AD) treated with dupilumab have an increased risk for cutaneous T-cell lymphoma (CTCL) compared with those not treated with dupilumab.

Major finding: Patients with AD who did vs did not receive dupilumab had a significantly higher risk of developing CTCL (odds ratio [OR] 4.1003; 95% CI 2.055-8.192). The risk for CTCL persisted in those with no prior exposure to disease-modifying antirheumatic drugs (OR 3.202; 95% CI 1.573-6.514).

Study details: This retrospective cohort study included patients with AD who did (n = 22,888) or did not (n = 22,871) receive dupilumab treatment and did not have a preexisting diagnosis for CTCL, Hodgkin lymphoma, non-Hodgkin lymphoma, nonfollicular lymphoma, leukemia, malignant melanoma, squamous cell carcinoma, or basal cell carcinoma.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Hasan I, Parsons L, Duran S, Zinn Z. Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study. J Am Acad Dermatol. 2024 (Apr 6). doi: 10.1016/j.jaad.2024.03.039 Source

Key clinical point: Patients with atopic dermatitis (AD) treated with dupilumab have an increased risk for cutaneous T-cell lymphoma (CTCL) compared with those not treated with dupilumab.

Major finding: Patients with AD who did vs did not receive dupilumab had a significantly higher risk of developing CTCL (odds ratio [OR] 4.1003; 95% CI 2.055-8.192). The risk for CTCL persisted in those with no prior exposure to disease-modifying antirheumatic drugs (OR 3.202; 95% CI 1.573-6.514).

Study details: This retrospective cohort study included patients with AD who did (n = 22,888) or did not (n = 22,871) receive dupilumab treatment and did not have a preexisting diagnosis for CTCL, Hodgkin lymphoma, non-Hodgkin lymphoma, nonfollicular lymphoma, leukemia, malignant melanoma, squamous cell carcinoma, or basal cell carcinoma.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Hasan I, Parsons L, Duran S, Zinn Z. Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study. J Am Acad Dermatol. 2024 (Apr 6). doi: 10.1016/j.jaad.2024.03.039 Source

Key clinical point: Patients with atopic dermatitis (AD) treated with dupilumab have an increased risk for cutaneous T-cell lymphoma (CTCL) compared with those not treated with dupilumab.

Major finding: Patients with AD who did vs did not receive dupilumab had a significantly higher risk of developing CTCL (odds ratio [OR] 4.1003; 95% CI 2.055-8.192). The risk for CTCL persisted in those with no prior exposure to disease-modifying antirheumatic drugs (OR 3.202; 95% CI 1.573-6.514).

Study details: This retrospective cohort study included patients with AD who did (n = 22,888) or did not (n = 22,871) receive dupilumab treatment and did not have a preexisting diagnosis for CTCL, Hodgkin lymphoma, non-Hodgkin lymphoma, nonfollicular lymphoma, leukemia, malignant melanoma, squamous cell carcinoma, or basal cell carcinoma.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Hasan I, Parsons L, Duran S, Zinn Z. Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study. J Am Acad Dermatol. 2024 (Apr 6). doi: 10.1016/j.jaad.2024.03.039 Source

Key clinical point: Established and new atopic dermatitis (AD)-associated filaggrin loss-of-function variants are associated with increased risks for clinical AD outcomes and disruption of skin barrier integrity in lesional and nonlesional skin of children with AD.

Major finding: Twenty variants were identified, including one novel variant. The presence of one or more variants was associated with a higher risk for moderate or severe AD vs mild AD (odds ratio 2.00; corrected P = .0394), a higher Scoring AD score (corrected P = .0394), and transepidermal water loss in both lesional (P = .018) and nonlesional (P = .015) skin.

Study details: This study included 438 children with AD (age ≤ 2 years; gestation period ≥ 36 weeks) from the early-life Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort without a comorbid lung condition or dependence on immunosuppression or oral steroids for a condition except asthma.

Disclosures: This study was funded by the US National Institutes of Health. Matthew S. Hestand declared being an employee and shareholder of Pacific Biosciences. The other authors declared no conflicts of interest.

Source: Virolainen SJ, Satish L, Biagini JM, et al. Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early life prospective cohort. JCI Insight. 2024 (Apr 2). doi: 10.1172/jci.insight.178258 Source

Key clinical point: Established and new atopic dermatitis (AD)-associated filaggrin loss-of-function variants are associated with increased risks for clinical AD outcomes and disruption of skin barrier integrity in lesional and nonlesional skin of children with AD.

Major finding: Twenty variants were identified, including one novel variant. The presence of one or more variants was associated with a higher risk for moderate or severe AD vs mild AD (odds ratio 2.00; corrected P = .0394), a higher Scoring AD score (corrected P = .0394), and transepidermal water loss in both lesional (P = .018) and nonlesional (P = .015) skin.

Study details: This study included 438 children with AD (age ≤ 2 years; gestation period ≥ 36 weeks) from the early-life Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort without a comorbid lung condition or dependence on immunosuppression or oral steroids for a condition except asthma.

Disclosures: This study was funded by the US National Institutes of Health. Matthew S. Hestand declared being an employee and shareholder of Pacific Biosciences. The other authors declared no conflicts of interest.

Source: Virolainen SJ, Satish L, Biagini JM, et al. Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early life prospective cohort. JCI Insight. 2024 (Apr 2). doi: 10.1172/jci.insight.178258 Source

Key clinical point: Established and new atopic dermatitis (AD)-associated filaggrin loss-of-function variants are associated with increased risks for clinical AD outcomes and disruption of skin barrier integrity in lesional and nonlesional skin of children with AD.

Major finding: Twenty variants were identified, including one novel variant. The presence of one or more variants was associated with a higher risk for moderate or severe AD vs mild AD (odds ratio 2.00; corrected P = .0394), a higher Scoring AD score (corrected P = .0394), and transepidermal water loss in both lesional (P = .018) and nonlesional (P = .015) skin.

Study details: This study included 438 children with AD (age ≤ 2 years; gestation period ≥ 36 weeks) from the early-life Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort without a comorbid lung condition or dependence on immunosuppression or oral steroids for a condition except asthma.

Disclosures: This study was funded by the US National Institutes of Health. Matthew S. Hestand declared being an employee and shareholder of Pacific Biosciences. The other authors declared no conflicts of interest.

Source: Virolainen SJ, Satish L, Biagini JM, et al. Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early life prospective cohort. JCI Insight. 2024 (Apr 2). doi: 10.1172/jci.insight.178258 Source