Clinical Edge Journal Scan

Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.

With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.

Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.

Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.

With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.

Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.

Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.

With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.

Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.

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

Key clinical point: Baricitinib treatment was effective and well-tolerated in patients with moderate to severe atopic dermatitis (AD) who were followed-up for 3 months in real-world settings.

Major finding: Baricitinib led to a significant reduction in the Eczema Area Severity Index (21.5 ± 13.2 vs 9.3 ± 9.0) and objective Scoring AD (45.9 ± 12.3 vs 28.2 ± 15.5) scores at 3 months vs start visit (both P < .001). The treatment discontinuation rate was 16.7%, with two patients discontinuing baricitinib due to adverse events.

Study details: This was an interim analysis of the TREATgermany registry that included 81 adult patients with moderate to severe AD who received baricitinib and concomitant topical treatment, of whom 49 had initiated baricitinib at a registry visit; 26 of these did not switch from a previous systemic drug and had their first follow-up visit at 3 months.

Disclosures: TREATgermany is supported by AbbVie Deutschland GmbH & Co. KG, Galderma S.A., and others. Six authors declared serving as consultants, lecturers, etc., for or having other ties with various organizations, including the sponsors of TREATgermany. The other authors declared no conflicts of interest.

Source: Traidl S, Heinrich L, Siegels D, et al, and the TREATgermany study group. Treatment of moderate-to-severe atopic dermatitis with baricitinib: Results from an interim analysis of the TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Mar 28). doi: 10.1111/jdv.19979 Source

Key clinical point: Baricitinib treatment was effective and well-tolerated in patients with moderate to severe atopic dermatitis (AD) who were followed-up for 3 months in real-world settings.

Major finding: Baricitinib led to a significant reduction in the Eczema Area Severity Index (21.5 ± 13.2 vs 9.3 ± 9.0) and objective Scoring AD (45.9 ± 12.3 vs 28.2 ± 15.5) scores at 3 months vs start visit (both P < .001). The treatment discontinuation rate was 16.7%, with two patients discontinuing baricitinib due to adverse events.

Study details: This was an interim analysis of the TREATgermany registry that included 81 adult patients with moderate to severe AD who received baricitinib and concomitant topical treatment, of whom 49 had initiated baricitinib at a registry visit; 26 of these did not switch from a previous systemic drug and had their first follow-up visit at 3 months.

Disclosures: TREATgermany is supported by AbbVie Deutschland GmbH & Co. KG, Galderma S.A., and others. Six authors declared serving as consultants, lecturers, etc., for or having other ties with various organizations, including the sponsors of TREATgermany. The other authors declared no conflicts of interest.

Source: Traidl S, Heinrich L, Siegels D, et al, and the TREATgermany study group. Treatment of moderate-to-severe atopic dermatitis with baricitinib: Results from an interim analysis of the TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Mar 28). doi: 10.1111/jdv.19979 Source

Key clinical point: Baricitinib treatment was effective and well-tolerated in patients with moderate to severe atopic dermatitis (AD) who were followed-up for 3 months in real-world settings.

Major finding: Baricitinib led to a significant reduction in the Eczema Area Severity Index (21.5 ± 13.2 vs 9.3 ± 9.0) and objective Scoring AD (45.9 ± 12.3 vs 28.2 ± 15.5) scores at 3 months vs start visit (both P < .001). The treatment discontinuation rate was 16.7%, with two patients discontinuing baricitinib due to adverse events.

Study details: This was an interim analysis of the TREATgermany registry that included 81 adult patients with moderate to severe AD who received baricitinib and concomitant topical treatment, of whom 49 had initiated baricitinib at a registry visit; 26 of these did not switch from a previous systemic drug and had their first follow-up visit at 3 months.

Disclosures: TREATgermany is supported by AbbVie Deutschland GmbH & Co. KG, Galderma S.A., and others. Six authors declared serving as consultants, lecturers, etc., for or having other ties with various organizations, including the sponsors of TREATgermany. The other authors declared no conflicts of interest.

Source: Traidl S, Heinrich L, Siegels D, et al, and the TREATgermany study group. Treatment of moderate-to-severe atopic dermatitis with baricitinib: Results from an interim analysis of the TREATgermany registry. J Eur Acad Dermatol Venereol. 2024 (Mar 28). doi: 10.1111/jdv.19979 Source

Key clinical point: Patients with atopic dermatitis (AD) have a significantly increased risk of developing lymphoma.

Major finding: Patients with AD vs control individuals showed a significantly increased likelihood of developing noncutaneous T-cell lymphoma (odds ratio [OR] 2.52; 95% CI 1.37-4.62), with similar outcomes for the peripheral T-cell lymphoma subtype (OR 4.00; 95% CI 1.50-10.66).

Study details: Findings are from a nested case-control study including 6425 adult patients with AD and 25,700 matched control individuals without AD from electronic health records.

Disclosures: This study did not receive any funding. Benjamin Ungar reported being an employee of Mount Sinai and receiving research funds from and serving as a consultant for various organizations.

Source: Powers CM, Piontkowski AJ, Orloff J, et al. Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database. J Am Acad Dermatol. 2024 (Apr 4). doi: 10.1016/j.jaad.2024.03.038 Source

Key clinical point: Patients with atopic dermatitis (AD) have a significantly increased risk of developing lymphoma.

Major finding: Patients with AD vs control individuals showed a significantly increased likelihood of developing noncutaneous T-cell lymphoma (odds ratio [OR] 2.52; 95% CI 1.37-4.62), with similar outcomes for the peripheral T-cell lymphoma subtype (OR 4.00; 95% CI 1.50-10.66).

Study details: Findings are from a nested case-control study including 6425 adult patients with AD and 25,700 matched control individuals without AD from electronic health records.

Disclosures: This study did not receive any funding. Benjamin Ungar reported being an employee of Mount Sinai and receiving research funds from and serving as a consultant for various organizations.

Source: Powers CM, Piontkowski AJ, Orloff J, et al. Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database. J Am Acad Dermatol. 2024 (Apr 4). doi: 10.1016/j.jaad.2024.03.038 Source

Key clinical point: Patients with atopic dermatitis (AD) have a significantly increased risk of developing lymphoma.

Major finding: Patients with AD vs control individuals showed a significantly increased likelihood of developing noncutaneous T-cell lymphoma (odds ratio [OR] 2.52; 95% CI 1.37-4.62), with similar outcomes for the peripheral T-cell lymphoma subtype (OR 4.00; 95% CI 1.50-10.66).

Study details: Findings are from a nested case-control study including 6425 adult patients with AD and 25,700 matched control individuals without AD from electronic health records.

Disclosures: This study did not receive any funding. Benjamin Ungar reported being an employee of Mount Sinai and receiving research funds from and serving as a consultant for various organizations.

Source: Powers CM, Piontkowski AJ, Orloff J, et al. Risk of lymphoma in patients with atopic dermatitis: A case-control study in the All of Us database. J Am Acad Dermatol. 2024 (Apr 4). doi: 10.1016/j.jaad.2024.03.038 Source

Key clinical point: Passive smoking during pregnancy is associated with an increased risk for atopic dermatitis (AD) in offspring; however, the association between active smoking during pregnancy and AD in offspring remains unestablished.

Major finding: Passive smoking during pregnancy led to a higher risk for AD in offspring (odds ratio [OR] 1.52; 95% CI 1.36-1.70); however, active smoking during pregnancy did not increase the risk for AD in offspring (OR 0.96; 95% CI 0.86-1.07).

Study details: This meta-analysis of 15 observational studies included children or mother-child pairs who underwent either questionnaire-based or physician assessment for AD diagnosis and questionnaire-based assessment or cotinine level measurement for evaluating exposure to active or passive smoking.

Disclosures: This study was supported by the Key Scientific and Technological Research Projects of Henan Province and the Key Scientific Research Projects in Universities of Henan Province, China. The authors declared no conflicts of interest.

Source: Chao L, Liang W, Zhao X, et al. Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2024 (Ma 14). doi: 10.1111/jdv.19958 Source

Key clinical point: Passive smoking during pregnancy is associated with an increased risk for atopic dermatitis (AD) in offspring; however, the association between active smoking during pregnancy and AD in offspring remains unestablished.

Major finding: Passive smoking during pregnancy led to a higher risk for AD in offspring (odds ratio [OR] 1.52; 95% CI 1.36-1.70); however, active smoking during pregnancy did not increase the risk for AD in offspring (OR 0.96; 95% CI 0.86-1.07).

Study details: This meta-analysis of 15 observational studies included children or mother-child pairs who underwent either questionnaire-based or physician assessment for AD diagnosis and questionnaire-based assessment or cotinine level measurement for evaluating exposure to active or passive smoking.

Disclosures: This study was supported by the Key Scientific and Technological Research Projects of Henan Province and the Key Scientific Research Projects in Universities of Henan Province, China. The authors declared no conflicts of interest.

Source: Chao L, Liang W, Zhao X, et al. Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2024 (Ma 14). doi: 10.1111/jdv.19958 Source

Key clinical point: Passive smoking during pregnancy is associated with an increased risk for atopic dermatitis (AD) in offspring; however, the association between active smoking during pregnancy and AD in offspring remains unestablished.

Major finding: Passive smoking during pregnancy led to a higher risk for AD in offspring (odds ratio [OR] 1.52; 95% CI 1.36-1.70); however, active smoking during pregnancy did not increase the risk for AD in offspring (OR 0.96; 95% CI 0.86-1.07).

Study details: This meta-analysis of 15 observational studies included children or mother-child pairs who underwent either questionnaire-based or physician assessment for AD diagnosis and questionnaire-based assessment or cotinine level measurement for evaluating exposure to active or passive smoking.

Disclosures: This study was supported by the Key Scientific and Technological Research Projects of Henan Province and the Key Scientific Research Projects in Universities of Henan Province, China. The authors declared no conflicts of interest.

Source: Chao L, Liang W, Zhao X, et al. Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2024 (Ma 14). doi: 10.1111/jdv.19958 Source

Key clinical point: In children with atopic dermatitis (AD), weekly vitamin D3 (VD3) supplementation vs placebo for 6 weeks failed to decrease the clinical severity of AD or alter type 2 immunity biomarkers.

Major finding: At 6 weeks, the change in the Severity Scoring of AD (SCORAD) index was similar in the VD3 (−5.3 ± 11.6) and placebo (−5.5 ± 9.9; P = .91) groups. No significant between-group differences were observed for change in type 2 immunity blood biomarkers, such as eosinophil counts, total immunoglobulin E (IgE), and specific IgE against staphylococcal enterotoxin A and B (all P > .05).

Study details: This randomized controlled trial included 101 children with AD (age 2-17 years) who were randomly assigned to receive weekly oral VD3 (8000, 12,000, and 16,000 IU for ages 2-5.9, 6-11.9, and 12-17.9 years, respectively; n = 53) or placebo (n = 48) for 6 weeks.

Disclosures: This study was funded by Fondo de Desarrollo Científico y Tecnológico, Chile. The authors declared no conflicts of interest.

Source: Borzutzky A, Iturriaga C, Pérez-Mateluna G, et al. Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial. J Eur Acad Dermatol Venereol. 2024 (Mar 14). doi: 10.1111/jdv.19959 Source

Key clinical point: In children with atopic dermatitis (AD), weekly vitamin D3 (VD3) supplementation vs placebo for 6 weeks failed to decrease the clinical severity of AD or alter type 2 immunity biomarkers.

Major finding: At 6 weeks, the change in the Severity Scoring of AD (SCORAD) index was similar in the VD3 (−5.3 ± 11.6) and placebo (−5.5 ± 9.9; P = .91) groups. No significant between-group differences were observed for change in type 2 immunity blood biomarkers, such as eosinophil counts, total immunoglobulin E (IgE), and specific IgE against staphylococcal enterotoxin A and B (all P > .05).

Study details: This randomized controlled trial included 101 children with AD (age 2-17 years) who were randomly assigned to receive weekly oral VD3 (8000, 12,000, and 16,000 IU for ages 2-5.9, 6-11.9, and 12-17.9 years, respectively; n = 53) or placebo (n = 48) for 6 weeks.

Disclosures: This study was funded by Fondo de Desarrollo Científico y Tecnológico, Chile. The authors declared no conflicts of interest.

Source: Borzutzky A, Iturriaga C, Pérez-Mateluna G, et al. Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial. J Eur Acad Dermatol Venereol. 2024 (Mar 14). doi: 10.1111/jdv.19959 Source

Key clinical point: In children with atopic dermatitis (AD), weekly vitamin D3 (VD3) supplementation vs placebo for 6 weeks failed to decrease the clinical severity of AD or alter type 2 immunity biomarkers.

Major finding: At 6 weeks, the change in the Severity Scoring of AD (SCORAD) index was similar in the VD3 (−5.3 ± 11.6) and placebo (−5.5 ± 9.9; P = .91) groups. No significant between-group differences were observed for change in type 2 immunity blood biomarkers, such as eosinophil counts, total immunoglobulin E (IgE), and specific IgE against staphylococcal enterotoxin A and B (all P > .05).

Study details: This randomized controlled trial included 101 children with AD (age 2-17 years) who were randomly assigned to receive weekly oral VD3 (8000, 12,000, and 16,000 IU for ages 2-5.9, 6-11.9, and 12-17.9 years, respectively; n = 53) or placebo (n = 48) for 6 weeks.

Disclosures: This study was funded by Fondo de Desarrollo Científico y Tecnológico, Chile. The authors declared no conflicts of interest.

Source: Borzutzky A, Iturriaga C, Pérez-Mateluna G, et al. Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial. J Eur Acad Dermatol Venereol. 2024 (Mar 14). doi: 10.1111/jdv.19959 Source