BACKGROUND:Lichenification, common in moderate to severe atopic dermatitis (AD) at any age, is often difficult to treat. This analysis assessed dupilumab vs placebo in AD lichenification by age and race-defined groups. METHODS:This post hoc analysis included pooled data from five clinical trials of dupilumab (NCT03054428, NCT03345914, NCT02277743, NCT02277769, NCT02395133), including 1,997 patients aged 6 to 88 years of all races with moderate to severe AD. RESULTS:Placebo/dupilumab randomized groups analyzed by age (n=1,535) included 123/244 children, 85/166 adolescents, and 460/457 adults; groups analyzed by self-reported racial background (n=1,902) included 132/234 Asian, 74/112 Black/African American, and 427/923 White patients. Dupilumab treatment resulted in nominally significant reductions vs placebo in Global Individual Signs Score lichenification from week 1 (adults/adolescents) or week 2 (children) through week 16. Lichenification measured by SCORing Atopic Dermatitis and Eczema Area and Severity Index improved similarly. By week 16, dupilumab significantly improved lichenification, with nominal significance vs placebo across all racial groups. CONCLUSION:Dupilumab treatment resulted in rapid and sustained improvement in lichenification across anatomic regions in all ages. Lichenification improved to a similar extent across racial groups. J Drugs Dermatol. 2025;24(2):167-173. doi:10.36849/JDD.8585R1.

Prurigo nodularis (PN) is a chronic, inflammatory skin condition characterized by multiple, intensely pruritic, distinctive nodular lesions. Subsequent scratching can further intensify the pruritus, culminating in a self-reinforcing itch-scratch cycle, which drives lesion development. The latest data indicate dysregulation of the neuroimmune axis in PN pathogenesis, including the involvement of sensory neurons, key effector immune cells, proinflammatory cytokines, dermal fibroblasts, and pruritogens. In this review, we highlight evidence supporting the role of type 2 immune axis dysregulation in driving the clinical presentation of PN and discuss how related signaling pathways may offer effective therapeutic targets to control PN signs and symptoms.

BACKGROUND:The prevalence and burden of atopic dermatitis (AD) are disproportionately high in people with skin of colour. Previous research has shown that the risk of xerosis and/or dyspigmentation is heightened in this population and may be more bothersome. However, no patient-reported instruments have been developed specifically for these disease sequelae in patients with skin of colour. OBJECTIVES:To develop and perform content validation of patient-reported outcome (PRO) questionnaires to assess AD-related xerosis and dyspigmentation in patients with skin of colour. METHODS:A targeted literature review was conducted to understand and identify AD-related disease sequelae and quality-of-life impacts relevant to patients with skin of colour and any instruments used to assess AD in the target population. Two draft PRO questionnaires assessing xerosis (X-AD) and dyspigmentation (D-AD) were developed and refined following advice meetings with three clinical experts. Questionnaire content validity was explored during hybrid concept elicitation and cognitive debriefing interviews with 15 adult and adolescent patients with skin of colour who have moderate-to-severe AD. RESULTS:Ten concept-focused articles, 3 websites, 17 labels, 1 U.S. Food and Drug Administration compendium and 1 clinical trial confirmed that xerosis and dyspigmentation are important AD-related disease sequelae. Patients with skin of colour [47% girls/women; mean (SD) age 33.3 (21.2) years] reported that the questionnaires were relevant to their AD experience in an appropriate recall timeframe and were readily understood, and that meaningful responses were easy to select. The final X-AD consisted of one 11-point numerical rating scale (NRS) assessing xerosis severity and two items assessing the level of bother associated with xerosis appearance and feeling over the past week (0-4 verbal rating scale). The final D-AD consisted of two 11-point NRS items assessing dyspigmentation severity and two items assessing the level of bother associated with how dyspigmentation looked over the past week. CONCLUSIONS:The X-AD/D-AD questionnaires were well understood and effective in capturing the experiences of xerosis and dyspigmentation in the target population in an appropriate and comprehensive way. This study supports the initial development of the questionnaires in accordance with regulatory guidelines and best practices; however, psychometric validation is required to evaluate the properties of each questionnaire and develop score interpretation guidelines.

Background:Despite advancements in the treatment landscape for psoriasis (PsO) and psoriatic arthritis (PsA), some patients may not achieve the desired disease improvement due to undertreatment. Understanding patient perspectives on treatment expectations can inform patient-centered decisions and enhance treatment satisfaction. Objective:To describe patient-identified treatment goals and expectations for managing psoriatic disease. Methods:A cross-sectional study was conducted using a survey through MyPsoriasisTeam, an online social community. The survey was available to its US-based patients aged ≥21 years with self-reported diagnoses of PsO and/or PsA. The study assessed patients' treatment goals, satisfaction with treatment outcomes, and satisfaction with health care providers (HCPs). Responses were summarized using descriptive statistics. Results:This analysis included 386 patients (PsO, n = 130; PsA with/without PsO, n = 256). Treatment goals varied by psoriatic disease type. The top 3 treatment goals for PsO were reduce itching (73.1%), reduction in size/thickness (68.5%), and reduction in the number of plaques (63.1), and for PsA, were reducing joint pain (77.7%), lessening fatigue (64.8%), and reducing joint stiffness (62.1%). Patient satisfaction with treatment outcomes was low (extremely/very satisfied: PsO, 7.5%/8.5% and PsA, 9.2%/20.2%). Overall, 73.1% with PsO were treated by a dermatologist, and a dermatologist or rheumatologist treated 74.6% with PsA. Overall, patient satisfaction with HCPs who treated their disease was lacking (PsO, 19.3% and 19.3%; PsA, 27.3% and 33.6% were extremely and very satisfied, respectively). Conclusion:These findings suggest the need for enhanced communication between patients and HCPs to align treatment goals and expectations and to improve treatment satisfaction and disease management.

Abstract Prurigo nodularis (PN) is a chronic inflammatory and pruritic skin disease. Clinically it is characterized by intense pruritus accompanied by hyperkeratotic nodules often associated with a very low quality of life including sleep disruption. The FDA has recently approved dupilumab as the only treatment for PN, but it is unknown to what extent within-patient categorical improvements in itch and skin lesions occurred concurrently or independently. Two phase 3 clinical trials, LIBERTY-PN PRIME and PRIME2, demonstrated dupilumab efficacy and safety in patients with PN. To report the efficacy of dupilumab on signs and symptoms in adult patients with PN who did and did not achieve the multicomponent endpoint. LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were randomized, double-blind, placebo-controlled, multicentre, parallel-group, phase 3 trials in adult patients with PN with ≥20 PN lesions and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Here, data were pooled from the two studies. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks for 24 weeks. This abstract assesses efficacy in patients who did and those who did not achieve the stringent multicomponent endpoint of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0–10) and Investigator’s Global Assessment PN Stage (IGA PN-S, score range: 0–4) score 0 or 1 (clear or almost clear; defined as 5 or fewer nodules) at week 24. Endpoints include a proportion of patients with concomitant ≥4-point reduction in WI-NRS from baseline and IGA PN-S score 0 or 1 at week 24; the proportion of patients with ≥4-point reduction in WI-NRS from baseline or IGA PN-S score 0 or 1 at week 24; and proportion of patients not achieving ≥4-point reduction in WI-NRS from baseline and IGA PN-S score 0 or 1 at week 24. Safety was also assessed. Baseline demographic and clinical characteristics were generally balanced between subgroups. The proportion of patients treated with dupilumab and placebo who achieved the multicomponent endpoints was 35.3% and 8.9%, respectively; and who achieved WI-NRS reduction of ≥4 points from baseline or IGA PN-S score 0 or 1 at week 24 was 69.9% and 27.2%, respectively. Among multicomponent nonresponders in the dupilumab group (n = 99), 36.4% achieved WI-NRS reduction of ≥4 points and 17.2% achieved IGA PN-S score 0 or 1; in the placebo group (n = 144), corresponding values were 11.1% and 9.0%, respectively. In the dupilumab group, 23.5% achieved only WI-NRS ≥4-point reduction from baseline at week 24, and 11.1% achieved only IGA PN-S score 0 or 1 at week 24. In the placebo group, corresponding data were 10.1%, and 8.2%, respectively. Safety findings were consistent with the known dupilumab safety profile. More than one-third of dupilumab-treated patients achieved the multicomponent endpoint at week 24, constituting concurrent responses on both itch and skin lesions. However, more than two-thirds had clinically meaningful improvement by week 24, defined as either ≥4-point reduction in WI-NRS from baseline, IGA PN-S score 0/1, or both. Almost one-quarter of dupilumab-treated patients met only WI-NRS ≥4-point improvement at week 24, suggesting that skin lesion improvement may lag behind the improvement of itch. Conversely, one-ninth met only IGA PN-S score of 0 or 1 at week 24 suggesting that, in addition to the overlapping mechanisms by which dupilumab ameliorates pruritus and skin lesions, there are independent treatment effects on itch and skin remodelling. Safety was consistent with the known safety profile of dupilumab across approved indications.

Dupilumab is the only FDA-approved systemic therapy for prurigo nodularis (PN), however, immunosuppressants (IS) and phototherapy have been used off-label for the treatment of this condition. Patients with prior IS/phototherapy treatment may represent a more severe and/or treatment-refractory population of patients with PN. Report post-hoc efficacy of dupilumab in patients with PN, with or without prior use of IS or phototherapy for PN. LIBERTY-PN PRIME and PRIME2 (NCT04183335 and NCT04202679) are randomized, 24-week, phase 3 studies in adults with PN that is inadequately controlled by topical prescription therapies or for whom those therapies are not advisable. Primary outcomes included a ≥4-point improvement in the weekly average of Worst Itch Numerical Rating Scale (WI-NRS) from baseline to week 24, and an Investigator’s Global Assessment for PN stage (IGA PN-S) score of 0/1 (clear/almost clear) at week 24. Safety outcomes included the incidence of treatment-emergent adverse events (TEAEs). Among patients with PN, 8.0% reported prior use of phototherapy, and 36.7% reported prior use of IS; overall, 126 (dupilumab group, n = 62; placebo group, n = 64) patients with and 185 (dupilumab, n = 91; placebo, n = 94) patients without prior IS/phototherapy use were included. A larger proportion of patients with prior treatment vs. patients without prior treatment had severe disease, as measured by IGA PN-S (40.5% vs. 29.0%). The baseline WI-NRS score (SD) for overall patients with prior treatment was 8.6 (1.0) and for patients without prior treatment was 8.4 (1.0). At week 24, 67.7% vs. 15.6% of patients in the dupilumab vs. placebo groups with prior treatment (odds ratio [95% confidence interval]: 13.6 [3.7–49.7]; P < 0.0001), and 52.7% vs. 21.3% of patients without prior treatment (5.8 [2.4–14.0]; P < 0.0001) achieved improvement in WI-NRS. Similarly, 35.5% vs. 10.9% (3.1 [1.2–8.4]; P = 0.0162) of patients with and 53.8% vs. 21.3% (5.0 [2.3–10.8]; P < 0.0001) of those without prior treatment achieved IGA PN-S score of 0/1, respectively. TEAEs were reported by 43 (69.4%) vs. 34 (53.1%) patients (dupilumab vs. placebo groups) with and 54 (60.0%) vs. 55 (59.1%) without prior treatment, respectively. Patients treated with dupilumab experienced a greater and clinically meaningful improvement in itch and achieved skin that was clear/almost clear of nodules at week 24, regardless of prior use of IS/phototherapy for the treatment of PN. The incidence of TEAEs was generally consistent among patients with and without prior IS/phototherapy.

The article by Labib et al 1 provides a valuable review of prurigo nodularis (PN).Dupilumab, recently approved by the U. S. Food and Drug Administration as the only systemic therapy for the treatment of PN, is mentioned among novel immunotherapies under investigation.Dupilumab safety is reviewed based on clinical trial data for atopic dermatitis (AD).However, the article cites skin infections as adverse reactions more commonly associated with dupilumab relative to placebo, a point that we believe warrants clarification.Eichenfield et al 2 analyzed pooled data from 7 randomized, placebo-controlled trials in adults with AD and found that the exposure-adjusted proportion of patients with treatment-emergent non-herpetic adjudicated skin infections was significantly lower with dupilumab than with placebo (14.5% vs 26.6%, p < 0.001).In the same study, the incidence of herpetic infections was non-significantly higher with dupilumab (12.7% vs 10.4%, p = 0.24), while eczema herpeticum and herpes zoster were significantly less frequent with dupilumab versus placebo (1.1% vs 3.6%, p = 0.004).Similarly, in a pooled analysis of 2 randomized, placebo-controlled trials in children aged 6-17 years with AD, Paller et al 3 reported significantly lower exposure-adjusted proportions of patients with total and nonherpetic skin infections in the dupilumab group versus placebo (respectively, 35.9% vs 67.0%, p = 0.001 and 27.8% vs 56.9%, p = 0.004), while herpes viral infections did not differ significantly (total herpes infections, 8.9% vs 14.7%, p = 0.262; eczema herpeticum, 0.8% vs 1.6%, p = 0.628; herpes zoster, 0.8% vs 0, p = 1.0).Additionally, Blauvelt et al 4 analyzed treatment-emergent infections over 4 years of dupilumab treatment in an AD open-label study and found that the cumulative number of patients with serious or severe infections, non-herpetic or herpetic infections, and total skin infections, decreased yearly with continued treatment.In PN, subsequent to the publication of Labib et al, 1 results from Phase 3 randomized LIBERTY-PN PRIME and PRIME2 trials showed, similarly to AD trials, that non-herpetic skin infections occurred less frequently in patients treated with dupilumab versus placebo (2.7% vs 9.3% in PRIME, and 5.2% vs 6.1% in PRIME2); herpetic skin infections did not occur in PRIME and were more frequent with dupilumab in PRIME2 (5.2% vs 0). 5 AD patients are highly susceptible to non-herpetic skin infections, usually with Gram-positive bacteria, and dupilumab was shown to decrease abundance of Staphylococcus aureus in both AD lesional and non-lesional skin, 6 results further supported by comprehensive evidence from clinical trials and post-marketing studies.Herpes infections are a known adverse drug reaction in both AD and PN and included in the U.S. prescribing information. 7n conclusion, evidence from AD and PN trials demonstrates that dupilumab treatment does not increase the risk of skin infections overall, and is associated with fewer non-herpetic skin infections compared with placebo.

Abstract Prurigo nodularis (PN) is characterized by the presence of itchy nodules on the trunk/extremities and is often accompanied by skin pain and sleep disruption. Patient needs are highest regarding symptom control and improvement of itch, which is one of the main hallmarks of PN. Using pooled blinded data from two randomized, double-blind, placebo-controlled phase III trials of dupilumab in adults with PN uncontrolled on topical therapies, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), the psychometric validation and within-patient meaningful change thresholds for three patient-reported outcome (PRO) instruments of the trial were assessed in patients with PN: Worst Itch Numerical Rating Scale (WI-NRS), Skin Pain-NRS and Sleep-NRS. The proportion of patients achieving clinically meaningful improvement in these PRO scores in LIBERTY-PN PRIME and PRIME2 was investigated in this post hoc analysis. Adults with PN inadequately controlled on topical prescription therapies, or when those therapies were not advisable, were randomized 1 : 1 to dupilumab 300 mg every 2 weeks or matched placebo. Here, we report the proportion of patients meeting a defined improvement threshold in weekly averages from baseline to week 24 of ≥ 4 points in WI-NRS, ≥ 4 points in Skin Pain-NRS and ≥ 2 points in Sleep-NRS (within-patient meaningful improvement thresholds defined in the context of the LIBERTY-PN PRIME and PRIME2 studies, range 0–10), and the proportion of patients who achieved a new composite endpoint, meaningful improvement in WI-NRS and either Skin Pain-NRS or Sleep-NRS at week 24. A total of 311 patients were randomized (dupilumab, n = 153; placebo, n = 158). Baseline scores for WI-NRS, Skin Pain-NRS and Sleep-NRS were balanced between treatment groups. Significantly more patients treated with dupilumab vs. placebo achieved in-­patient meaningful improvement in WI-NRS (58.8% vs. 19.0%; P < 0.001), Skin Pain-NRS (49.7% vs. 20.9%; P < 0.001) and Sleep-NRS (42.5% vs. 23.4%; P < 0.001) from baseline to week 24. More patients treated with dupilumab experienced clinically meaningful improvement in WI-NRS and either Skin Pain-NRS or Sleep-NRS vs. placebo (53.6% vs. 18.4%; P < 0.001). Adults with PN uncontrolled on topical therapies treated with dupilumab achieved statistically significant and clinically meaningful improvement in itch, skin pain and sleep quality individually, and in itch combined with either skin pain or sleep. The safety profile of dupilumab was consistent with the known safety profile in its approved indications. Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

Previous studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to < 12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis treated with dupilumab. In this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to < 15 kg: 200 mg; 15 kg to < 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided. No clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal. These results suggest that routine laboratory monitoring of children aged 6 months to < 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening. ClinicalTrials.gov: NCT03346434, part B Atopic dermatitis (AD) is a chronic, inflammatory skin disease that often causes itchy rashes. To reduce persistent AD signs and symptoms, patients may need to take medications that require laboratory monitoring. This can add to treatment burden, especially among infants and children. Dupilumab is a drug that specifically targets key molecules that underlie AD and has been tested in several clinical trials, now in patients 6 months and older. Studies in adults, adolescents, and children as young as 6 years of age with moderate-to-severe AD have shown that dupilumab can be used without the need for regular laboratory tests. In this study, the authors analyzed blood and urine samples collected during a clinical trial of dupilumab in 161 infants and children aged 6 months to 5 years with moderate-to-severe AD. Routine laboratory tests revealed no clinically meaningful changes in patients’ blood and urine following treatment with dupilumab. In general, the laboratory results in these patients were similar to those in adults, adolescents, and children aged 6–11 years treated with dupilumab. Taken together, these findings suggest that dupilumab can be used for the continuous treatment of moderate-to-severe AD without the need for routine laboratory monitoring.

Atopic dermatitis (AD) is characterized by epidermal dysfunction and interleukin (IL)-4/IL-13-predominant inflammation. Dupilumab, a monoclonal antibody that targets IL-4Rα, has demonstrated clinical efficacy/safety in AD. The skin barrier proteomic changes in AD patients with dupilumab treatment are not established. Longitudinal lesional and non-lesional skin tape stripping (STS) was performed for 20 healthy volunteers and 20 AD patients treated with dupilumab for 16 weeks. STS protein extracts were examined by liquid chromatography tandem mass spectrometry. Skin proteomic profiles were correlated with AD clinical parameters (SCORAD, EASI) and transepidermal water loss (TEWL AUC10). 490 proteins were detected in ≥80% of AD and healthy STS. 139 proteins were differentially expressed between AD and healthy individuals, 90 of which were significantly increased (cluster 1) (p<0.0001) and 49 were significantly reduced (cluster 2) (p<0.0001) in AD as compared to healthy skin in unsupervised cluster analysis at baseline. Functionally, cluster 1 proteins were enriched for markers of epidermal hyperplasia—intermediate keratin filaments (KRT6, KRT16, KRT17, KRT14, KRT5, DSP), glycolytic proteins (PKM, ALDOA, LDHA), proteins involved in actin filament organization (ACTB, ACT, TPM2), and protein translation (ribosomal subunits). Expression of these proteins significantly decreased in AD lesional skin with dupilumab treatment (p=0.0001) and approached levels seen in healthy skin at week 16. The decrease in expression of cluster 1 proteins in response to treatment significantly correlated with TEWL AUC10 decrease in AD lesional skin (r=0.73, p<0.001). Longitudinal proteomic assessment of dupilumab-treated AD skin established significant inhibition of epidermal hyperplasia markers, which correlated with significant improvements in TEWL.

Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. Data were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (< 60 [N = 2261] and ≥ 60 [N = 183] years). Patients received dupilumab 300 mg every week (qw) or every 2 weeks (q2w), or placebo with/without topical corticosteroids. Post hoc efficacy at week 16 was examined using broad categorical and continuous assessments of skin lesions, symptoms, biomarkers, and quality of life. Safety was also assessed. In the ≥ 60-year-old group at week 16, a greater proportion of dupilumab-treated patients achieved an Investigator’s Global Assessment score of 0/1 (q2w: 44.4

For children aged 6–11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator’s Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required. Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79

Abstract The objective of this analysis is to report the effect of dupilumab treatment on skin barrier function and patient-reported outcomes (PROs) in adults and adolescents with moderate-to-severe atopic dermatitis (AD). BALISTAD (NCT04447417) was an open-label trial in which transepidermal water loss (TEWL) was assessed repeatedly before and after skin tape stripping (STS) samples were taken from lesional and nonlesional skin of 26 patients with AD treated with dupilumab, and from normal skin of 26 matched healthy volunteers aged 12–65 years over a period of 16 weeks. PROs assessed included Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatological Life Quality Index [DLQI; for patients > 17 years old; Children’s DLQI (CDLQI) for patients aged > 12 to < 17 years]. At baseline, the median TEWL after five STS was statistically significantly higher in the lesional and nonlesional skin of patients with AD compared with healthy skin (P < 0.001 and P < 0.01, respectively) and statistically significantly decreased following dupilumab initiation as early as week 2 (P < 0.001 and P < 0.05, respectively). After 16 weeks of dupilumab treatment, there was no statistically significant difference in adjusted mean TEWL in AD lesional and nonlesional skin compared with matched healthy skin (P = 0.225 and P = 0.163, respectively). Significant improvement from baseline [mean (SD) change from baseline] was seen as early as week 2 in mean POEM [−8.4 (5.1)], DLQI [−5.3 (4.7)], CDLQI [−6.2 (4.7)] and PP-NRS [−2.2 (1.8); P < 0.001 and P < 0.05)] for CDLQI. Improvement was sustained through to week 16 [mean (SD) change from baseline; P < 0.001] for POEM [−13.6 (8.5)], DLQI [−8.6 (7.4)] and PP-NRS [−4.2 (2.6)] and with a P-value of < 0.01 for CDLQI [−9.2 (5.0)]. Dupilumab treatment normalizes epidermal barrier function in lesional and nonlesional skin in patients with moderate-to-severe AD, as measured with TEWL, and improves PROs. Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

BACKGROUND: Atopic dermatitis (AD) skin lesions are associated with oozing, bleeding, and erythema. This suggests that AD is associated with vascular changes. Dupilumab is an antibody to the alpha subunit of IL-4 receptor that demonstrates strong efficacy in the treatment of AD. IL-4 is known to reduce the permeability barrier function of vascular endothelium.OBJECTIVE: To examine the effects of dupilumab on vascular barrier function in AD skin.METHODS: Using proteomic analysis, we evaluated the plasma protein composition in skin tapes of lesional and nonlesional skin of adults and adolescents with moderate to severe AD over the course of a 16-week treatment with dupilumab and compared those with matched healthy subjects.RESULTS: At baseline, 115 plasma proteins were detected in AD skin and globally increased (1.5-fold or greater) compared with healthy skin. Functionally, these proteins included immunoglobulins, proteins involved in the coagulation process, enzymes, protease inhibitors, transport proteins, acute-phase proteins, complement proteins, and other pleiotropic proteins. Noteworthy, fibrinogens, fibronectin, and heme-binding proteins haptoglobin and hemopexin were among the top proteins originating from plasma and were increased in AD lesional versus healthy skin at baseline (P < .0001). Dupilumab treatment resulted in significantly reduced levels of plasma proteins in AD skin (P < .0001), with most dropping to levels seen in healthy skin or no longer detectable at week 16.CONCLUSIONS: Inhibition of IL-4/IL-13 action by dupilumab significantly reduces the efflux of plasma proteins into AD skin. Several of these proteins, such as fibrinogens and fibronectin, are known to enhance Staphylococcus aureus colonization and are associated with AD skin severity. (c) 2023 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:1421-8)

Introduction (context of the research) Previous analyses based on short-term, phase 2 studies reported that baseline biomarkers do not correlate with clinical outcomes following dupilumab treatment in patients with atopic dermatitis (AD). Objective To report whether pre-treatment levels of common serum biomarkers can predict treatment response to dupilumab in adults with moderate-to-severe AD using data from a new analysis based on 16-week, phase 3 studies. Methods LIBERTY AD SOLO 1 and 2 (NCT02277743, NCT02277769), two randomized, double-blind studies, included patients ≥ 18 years-old with moderate-to-severe AD treated with dupilumab 300mg every 2 weeks or placebo for 16 weeks. Correlation between change in Eczema Area and Severity Index (EASI) and log of baseline IgE, CC chemokine ligand 17 (CCL17; previously referred to as thymus and activation-regulated chemokine [TARC]) and lactate dehydrogenase (LDH) at baseline was assessed using Spearman's correlation coefficient (ρ). Results At Week 16, change in EASI showed little correlation with baseline total IgE (Spearman's correlation coefficient [ρ]=–0.14, n = 370 for dupilumab; ρ=–0.03, n = 202 for placebo), baseline CCL17 (ρ=–0.28, n=369 for dupilumab; ρ=–0.05, n=201 for placebo), or baseline LDH (ρ=–0.30, n=370 for dupilumab; ρ=–0.08, n=202 for placebo). Overall safety was consistent with the known dupilumab safety profile. Conclusions Baseline levels of total IgE, CCL17 and LDH do not predict treatment response to dupilumab, as measured by EASI, in adults with moderate-to-severe AD.

Background: Dupilumab inhibits signaling of IL-4 and IL-13 and has demonstrated efficacy for treatment of atopic dermatitis (AD). IL-4 and IL-13 are known to play roles in skin barrier function. This study explores the effects of dupilumab on skin barrier function in patients with AD.

Atopic dermatitis (AD) is heterogeneous in distribution pattern and clinical features. This analysis assessed the effect of dupilumab on the extent and severity of AD across various signs (erythema, edema/papulation, excoriation, lichenification) in different anatomical regions (head and neck, trunk, upper extremities, lower extremities) in patients aged 6 months to 5 years. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo with concomitant low-potency topical corticosteroids (TCS) every 4 weeks for 16 weeks. Changes in AD signs across anatomical regions were assessed using unweighted Eczema Area and Severity Index (EASI) body region scores. Overall, 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). A significant improvement in least squares mean EASI area score was seen by week 2 in all four anatomical regions (P < 0.0001 for dupilumab vs. placebo) and sustained throughout treatment. Least squares mean EASI sign scores in erythema, excoriations, and infiltration/papulation showed significant improvement by week 2 in all regions (P < 0.001), while lichenification showed significant improvement in all regions by week 4 (P < 0.001). Dupilumab use with concomitant low-potency TCS treatment resulted in rapid and consistent improvement in AD signs in all anatomical regions, in patients aged 6 months to 5 years with moderate-to-severe AD. ClinicalTrials.gov Identifier: NCT03346434 Part B.