Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity. OBJECTIVES: This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab. METHODS: Participants (n = 71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple time points: S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping. RESULTS: At baseline, 100% of participants were S aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S aureus after only 3 days (compared to placebo), which was 11 days before clinical improvement. Participants with the greatest S aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S aureus cytotoxins (day 7), perturbations in TH17-cell subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil, and complement pathways (day 7) were also observed. CONCLUSIONS: Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, and this reduction correlates with reductions in the type 2 biomarker, CCL17, and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for TH17 cells, neutrophils, and complement activation as potential mechanisms to explain these findings.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s). RESULTS: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE.

BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486.

Janus kinase inhibitors for treatment of morphea and systemic sclerosis: A literature review.

Morphea and systemic sclerosis (SSc) are rare disorders of connective tissue characterized by increased skin thickness and fibrosis, with current treatment options having variable efficacies, many with limited therapeutic benefit. Janus kinase (JAK) inhibitors have been shown in preclinical studies to inhibit the fibrotic pathway in murine models of systemic sclerosis, by blocking TGF-beta mediated pathway of STAT protein activation. Additionally, case reports of the treatment of morphea and SSc with tofacitinib, a JAK 1/3 inhibitor, have shown improvement in skin sclerosis. Several JAK inhibitors have been developed and utilized in dermatologic and rheumatologic diseases. To date, tofacitinib has been by far the most commonly trialed JAK inhibitor in patients with SSc and morphea. Herein we review the preclinical studies reported in the literature supporting the use and efficacy of JAK inhibitors for the treatment of morphea and the cutaneous manifestations of SSc, as well as discuss the clinical cases published to date illustrating the benefits of JAK inhibitors in disease management. The pathogenesis and mechanism of action will be reviewed as it relates to the process of skin fibrosis in morphea and SSc, along with the murine models illustrating efficacy of JAK inhibitors in fibrotic disease. Based on available preclinical and clinical data as well as consideration of the mechanism of action of JAK inhibitors on the pathway for cutaneous fibrosis, there is promising evidence to support the use and further study of JAK inhibitors in the management of morphea and cutaneous fibrosis in SSc.

Skin barrier defects in atopic dermatitis: From old idea to new opportunity.

Atopic dermatitis (AD) is the most common chronic skin inflammatory disease, with a profound impact on patients' quality of life. AD varies considerably in clinical course, age of onset and degree to which it is accompanied by allergic and non-allergic comorbidities. Skin barrier impairment in both lesional and nonlesional skin is now recognized as a critical and often early feature of AD. This may be explained by a number of abnormalities identified within both the stratum corneum and stratum granulosum layers of the epidermis. The goal of this review is to provide an overview of key barrier defects in AD, starting with a historical perspective. We will also highlight some of the commonly used methods to characterize and quantify skin barrier function. There is ample opportunity for further investigative work which we call out throughout this review. These include: quantifying the relative impact of individual epidermal abnormalities and putting this in a more holistic view with physiological measures of barrier function, as well as determining whether these barrier-specific endotypes predict clinical phenotypes (e.g. age of onset, natural history, comorbidities, response to therapies, etc). Mechanistic studies with new (and in development) AD therapies that specifically target immune pathways, Staphylococcus aureus abundance and/or skin barrier will help us understand the dynamic crosstalk between these compartments and their relative importance in AD.

Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum.

BACKGROUND: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+). METHODS: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation. RESULTS: Eight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR). CONCLUSION: SIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.

Eruptive agminated nevi in a successfully treated Langerhans cell histiocytosis patient.

A 7-year-old girl with a history of Langerhans cell histiocytosis (LCH), in remission, presented with the sudden appearance of multiple, agminated nevi. Skin biopsy revealed a benign junctional nevus, without recurrence of LCH. Subsequent immunohistochemical testing of both the skin and iliac wing biopsies demonstrated a BRAF V600E mutation. MAPK pathway mutations have been implicated in both LCH and nevogenesis.

Topical doxycycline monohydrate hydrogel 1% targeting proteases/PAR2 pathway is a novel therapeutic for atopic dermatitis.

Atopic Dermatitis (AD) is characterized by skin barrier disruption and an aberrant immune response. Doxycycline is tetracycline antibiotics broadly used systemically to treat inflammatory dermatologic conditions. Several studies have shown doxycycline has anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. It is our hypothesis that daily application of a novel doxycycline topical formulation in AD subjects will reduce severity of the disease, by blocking cutaneous proteases activity and restoring skin barrier function and inflammation. To test this hypothesis, we performed a proof of concept, open-label clinical study. Subjects enrolled in the study (n = 15) applied NanoDOX® Hydrogel 1% daily for 4 weeks on a chosen eczematous area. Investigational drug was well tolerated, and no local or systemic adverse events due to investigational drug were reported. Notably, a significant clinical improvement was observed based on a modified Eczema Area & Severity Index (EASI) score of the treated area from start of treatment to 14 and 28 days post-treatment (P < .001). A significant improvement of pruritus was also observed (P = .02). This proof of concept clinical trial is first to explore the impact of a non-systemic doxycycline treatment on AD patients. Our results provide evidence to investigate novel AD treatment strategies targeting cutaneous proteases activity.

Update on protease-activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases.

Protease-activated receptor 2 (PAR2) is a transmembrane receptor expressed by multiple tissues, including skin, with rapidly expanding knowledge regarding its roles. In the skin, PAR2 has extensively documented effects in promoting Th2 inflammation and pruritus; and its role in atopic dermatitis continues to be thoroughly studied. Numerous new investigations have shown a more complex range of activities potentially related to dermatologic diseases. Goal of this review is to outline emerging effects of PAR2 activation in the skin other than those related to immunologic and pruritic functions. Specifically, this work seeks to summarize current knowledge (and gaps) of PAR2 as a regulator of epidermal barrier, keratinocyte differentiation, cutaneous tumorigenesis and pigmentation. Additional focus will be placed on possible involvement in dermatologic disease and emergence as a therapeutic target.

Allergen Immunotherapy and Atopic Dermatitis: the Good, the Bad, and the Unknown.

PURPOSE OF REVIEW: In light of the recent advancements in atopic dermatitis treatment, this review aims to summarize the utility and efficacy of allergy immunotherapy in atopic dermatitis patients. We examine its mechanism, pathophysiology, cost-efficacy, and current guidelines for clinical practice. RECENT FINDINGS: The literature supports the use of allergy immunotherapy in atopic conditions such as allergic rhinitis and asthma but insufficient evidence exists to suggest its efficacy in atopic dermatitis. The use of allergy immunotherapy has been shown to provide long-term cost savings in both the USA and the European Union in certain populations but differences in prescribing patterns and manufacturing make it difficult to study its impact on a larger, generalizable scale. Conflicting meta-analyses data and conclusions highlight the need for better, higher quality research to better understand allergy immunotherapy utility in atopic dermatitis.

Collagenous and elastotic marginal plaques of the hand: A potential clue to the diagnosis of alkaptonuria.

Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic keratoderma characterized by hyperkeratotic linear plaques located along the radial and ulnar aspects of the hands bilaterally. As an isolated finding, CEMPH occurs secondarily to chronic trauma and photodamage. Herein, CEMPH is described as a manifestation of alkaptonuria (AKU). In addition to keloidal collagen, ochronotic fibers and fragmented, thickened elastic fibers were observed. Additionally, mucin deposition-not previously described in this clinical context-was also identified. Given their overlapping clinicopathologic features, CEMPH due to AKU should be distinguished from the acquired variant as well as acrokeratoelastoidosis.

The use of selective Th2 blocker dupilumab for the treatment of atopic dermatitis in a heart transplant patient: Case report.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsing eczematous rash with severe pruritus and recurrent infection. Topical emollients and immune-modulators (e.g., corticosteroids and calcineurin inhibitor) are first-line therapies for acute flares. In severe refractory cases, systemic immunosuppression may be required. Increased incidence of AD has been documented in heart-transplant children who receive their transplant or thymectomy before the age of 1 year. The treatment of these patients remains a conundrum for dermatologists. We present a case report of a chronically immunosuppressed transplant patient with severe AD treated with dupilumab and in remission for over 2 years with minimal side effects. We will also discuss impact of transplant immunosuppression in the pathogenesis of AD.

Antagonistic Effects of IL-4 on IL-17A-Mediated Enhancement of Epidermal Tight Junction Function.

Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease. AD is typically characterized by skewed T helper (Th) 2 inflammation, yet other inflammatory profiles (Th1, Th17, Th22) have been observed in human patients. How cytokines from these different Th subsets impact barrier function in this disease is not well understood. As such, we investigated the impact of the canonical Th17 cytokine, IL-17A, on barrier function and protein composition in primary human keratinocytes and human skin explants. These studies demonstrated that IL-17A enhanced tight junction formation and function in both systems, with a dependence on STAT3 signaling. Importantly, the Th2 cytokine, IL-4 inhibited the barrier-enhancing effect of IL-17A treatment. These observations propose that IL-17A helps to restore skin barrier function, but this action is antagonized by Th2 cytokines. This suggests that restoration of IL-17/IL-4 ratio in the skin of AD patients may improve barrier function and in so doing improve disease severity.

The cutaneous innate immune response in patients with atopic dermatitis.

Orchestrating when and how the cutaneous innate immune system should respond to commensal or pathogenic microbes is a critical function of the epithelium. The cutaneous innate immune system is a key determinant of the physical, chemical, microbial, and immunologic barrier functions of the epidermis. A malfunction in this system can lead to an inadequate host response to a pathogen or a persistent inflammatory state. Atopic dermatitis is the most common inflammatory skin disorder and characterized by abnormalities in both skin barrier structures (stratum corneum and tight junctions), a robust T(H)2 response to environmental antigens, defects in innate immunity, and an altered microbiome. Many of these abnormalities may occur as the consequence of epidermal dysfunction. The epidermis directly interfaces with the environment and, not surprisingly, expresses many pattern recognition receptors that make it a key player in cutaneous innate immune responses to skin infections and injury. This review will discuss the role epidermal innate receptors play in regulation of skin barriers and, where possible, discuss the relevance of these findings for patients with atopic dermatitis.

Efficacy and Safety of Dupilumab Maintained in Adults ≥ 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials.

BACKGROUND: Adults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety. OBJECTIVE: The aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD. METHODS: 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. RESULTS: 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%; qw: 39.7%) and 75% improvement in Eczema Area and Severity Index (63.0%; 61.6%) versus placebo (7.1% and 14.3%, respectively; P < 0.0001). Type 2 inflammation biomarkers (immunoglobulin E and thymus and activation-regulated chemokine) were also significantly reduced in dupilumab- versus placebo-treated patients (P < 0.01). Results were similar in the < 60-year-old group. The exposure-adjusted incidences of adverse events in dupilumab-treated patients were generally similar to those receiving placebo, with numerically fewer treatment-emergent adverse events in the dupilumab-treated ≥ 60-year-old group versus placebo. LIMITATIONS: There were fewer patients in the ≥ 60-year-old group; post hoc analyses. CONCLUSION: Dupilumab improved AD signs and symptoms in patients aged ≥ 60 years; results were comparable to those in patients aged < 60 years. Safety was consistent with the known dupilumab safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02277743, NCT02277769, NCT02755649, NCT02260986. Does dupilumab benefit adults aged 60 years and older with moderate-to-severe atopic dermatitis?(MP4 20,787 KB).