Burden of Atopic Dermatitis in Pediatric Patients: An International Cross-sectional Study.

BACKGROUND: Few large-scale international studies broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents. OBJECTIVE: To better characterize the AD burden in pediatric subjects by disease severity. METHODS: This cross-sectional, web-based survey of pediatric subjects (6 months to <18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Subjects with diagnosed AD were identified based on the International Study of Asthma and Allergies in Childhood criteria and self-/parent-report of ever being told by a physician that they/their child had eczema. AD severity was assessed using Patient Oriented Eczema Measure and Patient Global Assessment. Outcomes included measures of itch, skin pain, sleep, health-related quality-of-life (HRQoL), missed school days, and atopic comorbidities. RESULTS: The survey included 1489 children 6 months to < 6 years; 2898 children 6 to < 12 years; and 3078 adolescents 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, pediatric subjects with moderate or severe AD had more itch, skin pain, sleep problems, and impaired HRQoL, and missed more school days relative to those with mild AD; greater burden was observed among severe relative to moderate AD. At least one atopic comorbidity was present in 92·5% of all respondents. CONCLUSIONS: These results highlight the burden of AD in pediatric subjects especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life.

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis.

INTRODUCTION: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6-11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. METHODS: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6-11 years with severe AD. These included test-retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. RESULTS: The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. CONCLUSIONS: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6-11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3-4-point change in the Worst Itch Scale score. TRIAL REGISTRATION: NCT03345914. Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings?

The Family Impact of Atopic Dermatitis in the Pediatric Population: Results from an International Cross-sectional Study.

OBJECTIVE: To evaluate the impact of atopic dermatitis on families of pediatric patients. STUDY DESIGN: This cross-sectional, web-based survey of children/adolescents (6 months to <18 years old) with atopic dermatitis and their parents and caregivers was conducted in 18 countries encompassing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Children and adolescents with atopic dermatitis and their parents and caregivers were identified by the International Study of Asthma and Allergies in Childhood criteria and ever being told by a physician that they had "eczema". Atopic dermatitis severity was assessed using the Patient-Oriented Eczema Measure and the Patient Global Assessment. Atopic dermatitis impact on families' lives was evaluated using the Dermatitis Family Impact questionnaire and stand-alone questions on hours of atopic dermatitis-related care (past week) and missed work days (past 4 weeks) owing to their child's atopic dermatitis. RESULTS: A total of 7465 pairs of pediatric participants with atopic dermatitis and their parents or caregivers were surveyed. Across age groups, the Dermatitis Family Impact questionnaire total score for all regions ranged from 7.1 to 8.6, 13.2 to 14.9, and 17.0 to 17.2 for Patient-Oriented Eczema Measure mild, moderate, and severe atopic dermatitis, respectively. Subscale scores showed that greater atopic dermatitis severity had a greater impact on all family life domains, including sleep and tiredness. No specific patterns or trends were observed across age groups. Time spent on childcare and missed work days increased with atopic dermatitis severity. CONCLUSIONS: Across pediatric age groups and geographic regions, greater atopic dermatitis severity was associated with a greater negative impact on physical, emotional, social, and economic components of family life.

Treatment Outcomes Associated With Dupilumab Use in Patients With Atopic Dermatitis: 1-Year Results From the RELIEVE-AD Study.

IMPORTANCE: Clinical trial populations may not reflect clinical practice: knowledge generated in other settings can inform clinical decision-making. OBJECTIVE: To evaluate self-reported disease control and quality of life after initiating dupilumab treatment in patients with atopic dermatitis (AD) in the the clinical setting. DESIGN, SETTING, AND PARTICIPANTS: This cohort study using an online survey administered prior to (baseline) and at 1, 2, 3, 6, 9, and 12 months after dupilumab initiation included adults with moderate-to-severe AD who initiated treatment with dupilumab through the US patient support program and agreed to participate in the study. Data were collected between January 2018 and January 2020 and the analysis was completed in May 2020. INTERVENTIONS: Clinically driven treatment with dupilumab. MAIN OUTCOMES AND MEASURES: Disease control measured by the Atopic Dermatitis Control Tool (ADCT); concomitant AD therapies; satisfaction with therapy; skin symptoms (skin pain/soreness, hot/burning feeling, sensitivity to touch) assessed using numerical rating scales; flares; health-related quality of life assessed using the Dermatology Life Quality Index; sleep problems assessed using the ADCT item and a stand-alone question; and the AD-specific Work Productivity and Activity Impairment Questionnaire. RESULTS: Of 699 patients who initiated dupilumab (431 [61.7%] female, 515 [73.7%] White), 632 and 483 completed the survey at months 1 and 12, respectively. As-observed results showed that most patients achieved adequate disease control (ADCT total score) at month 1 with further improvement at month 12 (385 of 632 patients [60.9%] and 374 of 483 [77.4%] for the 2 time points, respectively, vs 41 of 699 [5.3%] at baseline; both P < .001). Use of other AD therapies was reduced at each follow-up vs baseline, including topical and systemic corticosteroids, which were reduced at month 12 to 40.4% (195 of 483 patients) and 6.2% (30 of 483 patients), respectively, from 68.1% (476 of 699) and 34.9% (244 of 699), respectively, at baseline (both P < .001 vs baseline). Patient satisfaction with AD treatment was higher than baseline (120 of 699 [17.7%]) at each follow-up to 85.1% (411 of 483) at month 12 (P < .001). At each follow-up, patients reported reductions in flares, itch, skin symptoms, and improved sleep, health-related quality of life, and daily activities vs baseline. Results were consistent based on observed data and imputed data using pattern mixture models for missing data. CONCLUSIONS AND RELEVANCE: Consistent with patient-reported outcomes in clinical trials, this cohort study found that dupilumab treatment was associated with rapid and sustained disease control for up to 12 months as demonstrated by statistically significant improvements relative to baseline on all patient-reported outcomes including treatment satisfaction.

The Use of Real-World Data to Evaluate the Association Between Atopic Dermatitis and Cardiovascular Disease: A Retrospective Claims Analysis.

INTRODUCTION: Atopic dermatitis (AD) is a systemic inflammatory condition that may increase the risk of cardiovascular disease (CVD); however, ongoing debate exists surrounding its direct association. We aimed to elucidate whether AD contributes to a higher incidence of CVD and major adverse cardiovascular events (MACE) in adult patients with AD, independent of metabolic disorders. METHODS: We retrospectively analyzed a large US-based population of patients with AD (≥ 18 years of age). Logistic regression estimated the risk of CVD and MACE in adult patients with AD, independent of metabolic disorders (including diabetes, hypertension, and obesity). RESULTS: The odds ratio (OR; 95% confidence interval [CI]) for patients without metabolic disorders was 1.25 (1.13, 1.39) for CVD and 1.22 (1.01, 1.47) for MACE. The OR (95% CI) for AD patients with metabolic disorders was 1.09 (1.07, 1.12) for CVD and 1.14 (1.09, 1.18) for MACE. This trend was even more pronounced after long-term follow-up (≥ 3 years). Lifestyle and health behavioral factors of the subjects were not available in the dataset. The lack of control for these factors could potentially confound our results. CONCLUSIONS: Atopic dermatitis may contribute to the risk of developing CVD and MACE in adults, independent of metabolic disorders.

Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study.

BACKGROUND: Little is known on the current global prevalence of atopic dermatitis (AD) in the pediatric population. OBJECTIVE: To estimate the real-world global prevalence of AD in the pediatric population and by disease severity. METHODS: This international, cross-sectional, web-based survey of children and adolescents (6 months to <18 years old) was conducted in the following 18 countries: North America (Canada, United States), Latin America (Argentina, Brazil, Columbia, Mexico), Europe (France, Germany, Italy, Spain, United Kingdom), Middle East and Eurasia (Israel, Saudi Arabia, Turkey, United Arab Emirates, Russia), and East Asia (Japan, Taiwan). Prevalence was determined using the following 2 definitions: (1) diagnosed as having AD according to the International Study of Asthma and Allergies in Childhood (ISAAC) criteria and self- or parent-report of ever being told by a physician that they or their child child had AD (eczema); and (2) reported AD based on the ISAAC criteria only. Severity was assessed using the Patient Global Assessment (PtGA) and Patient-Oriented Eczema Measure (POEM). RESULTS: Among 65,661 responders, the 12-month diagnosed AD prevalence (ISAAC plus self-reported diagnosis) ranged from 2.7% to 20.1% across countries; reported AD (ISAAC only) was 13.5% to 41.9%. Severe AD evaluated with both PtGA and POEM was generally less than 15%; more subjects rated AD as mild on PtGA than suggested by POEM. No trends in prevalence were observed based on age or sex; prevalence was generally lower in rural residential settings than urban or suburban. CONCLUSION: This global survey in 18 countries revealed that AD affects a substantial proportion of the pediatric population. Although prevalence and severity varied across age groups and countries, less than 15% had severe AD.

Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis.

BACKGROUND: Dupilumab has demonstrated efficacy with acceptable safety in clinical trials in patients with moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess dupilumab's impact on asthma and sinonasal conditions in adult patients with moderate to severe AD in four randomized, double-blinded, placebo-controlled trials. METHODS: In LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649), patients received placebo, dupilumab 300 mg every 2 weeks (q2w), or dupilumab 300 mg weekly (qw). In CHRONOS and CAFÉ, patients received concomitant topical corticosteroids. This post hoc analysis assessed Asthma Control Questionnaire-5 (ACQ-5) scores in patients with asthma, Sino-Nasal Outcome Test-22 (SNOT-22) scores in patients with sinonasal conditions, and AD signs and symptoms in all patients. RESULTS: Of the 2444 patients, 463 had asthma with baseline ACQ-5 ≥ 0.5 (19%); 1171 had sinonasal conditions (48%); and 311 had both (13%). At week 16, ACQ-5 scores (least squares mean change from baseline [standard error]) improved by 0.27 (0.07), 0.59 (0.08), and 0.56 (0.07) in placebo-, q2w-, and qw-treated patients with asthma, respectively, whereas SNOT-22 scores improved by 5.1 (0.8), 9.9 (0.9), and 10.8 (0.8) in patients with sinonasal conditions (P < .01 for all dupilumab vs placebo). Improvements in ACQ-5 and SNOT-22 were also seen in patients with both conditions. Dupilumab also significantly improved AD signs and symptoms among all subgroups. CONCLUSIONS: In this first analysis of patients with comorbid moderate to severe AD, asthma, and/or chronic sinonasal conditions, dupilumab improved all three diseases in a clinically meaningful and statistically significant manner (vs placebo), based on validated outcome measures.

Real-world persistence with dupilumab among adults with atopic dermatitis.

BACKGROUND: The real-world persistence with dupilumab therapy for atopic dermatitis (AD) is unknown. OBJECTIVE: To characterize adults with AD who initiated dupilumab and evaluate persistence with dupilumab therapy. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare database. Adults with AD who initiated dupilumab (first dispensation = index date) between March 28, 2017, and March 31, 2018, were identified and followed up until September 30, 2018, or disenrollment. Twelve months of continuous preindex enrollment were required to characterize baseline treatment history and comorbidities. Kaplan-Meier analysis was used to estimate dupilumab persistence at 6 and 12 months, assuming a 14-day injection frequency and a 30-day grace period. RESULTS: A total of 1963 adults were identified who initiated dupilumab (mean [SD] age 42.1 [15.7] years; 50.7% women; 49.8% with ≥1 atopic comorbidity). Baseline AD treatments included topical corticosteroids (81.6%), systemic corticosteroids (72.5%), and systemic immunosuppressants (22.8%). Dupilumab persistence (95% confidence interval) at 6 and 12 months was 91.9% (90.7%-93.2%) and 77.3% (75.0%-79.7%), respectively. Among 329 patients who discontinued dupilumab, the risk of reinitiation was 78.8% (95% confidence interval: 75.8%-81.7%) within an average of 4 months. CONCLUSION: Dupilumab persistence at 12 months was high, suggesting patient satisfaction with effectiveness, tolerability, and treatment regimen.

Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials.

BACKGROUND: Pain is a frequent symptom of atopic dermatitis (AD). OBJECTIVES: The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes. METHODS: This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD. RESULTS: Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%-33.1%) to 42.2% (95% confidence interval = 26.6%-57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate. CONCLUSIONS: Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.Trial Registration: ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

Effects of variations in access to care for children with atopic dermatitis.

BACKGROUND: An estimated 50% of children in the US are Medicaid-insured. Some of these patients have poor health literacy and limited access to medications and specialty care. These factors affect treatment utilization for pediatric patients with atopic dermatitis (AD), the most common inflammatory skin disease in children. This study assesses and compares treatment patterns and healthcare resource utilization (HCRU) between large cohorts of Medicaid and commercially insured children with AD. METHODS: Pediatric patients with AD were identified from 2 large US healthcare claims databases (2011-2016). Included patients had continuous health plan eligibility for ≥6 months before and ≥12 months after the first AD diagnosis (index date). Patients with an autoimmune disease diagnosis within 6 months of the index date were excluded. Treatment patterns and all-cause and AD-related HCRU during the observation period were compared between commercially and Medicaid-insured children. RESULTS: A minority of children were evaluated by a dermatology or allergy/immunology specialist. Several significant differences were observed between commercially and Medicaid-insured children with AD. Disparities detected for Medicaid-insured children included: comparatively fewer received specialist care, emergency department and urgent care center utilization was higher, a greater proportion had asthma and non-atopic morbidities, high- potency topical corticosteroids and calcineurin inhibitors were less often prescribed, and prescriptions for antihistamines were more than three times higher, despite similar rates of comorbid asthma and allergies among antihistamine users. Treatment patterns also varied substantially across physician specialties. CONCLUSIONS: Results suggest barriers in accessing specialty care for all children with AD and significant differences in management between commercially and Medicaid-insured children. These disparities in treatment and access to specialty care may contribute to poor AD control, especially in Medicaid-insured patients.

Correction to: Qualitative Assessment of Adult Patients' Perception of Atopic Dermatitis Using Natural Language Processing Analysis in a Cross-Sectional Study.

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Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate to severe atopic dermatitis: Analysis of the randomized phase 3 studies SOLO 1 and SOLO 2, AD ADOL, and CHRONOS.

BACKGROUND: Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD). OBJECTIVE: To evaluate the timing and effect of dupilumab on itch. METHODS: Analysis of data from 1505 patients with moderate to severe AD included in 4 randomized controlled studies, treated for up to 52 weeks. Adults received dupilumab 300 mg every 2 weeks or placebo monotherapy (SOLO 1: NCT02277743; SOLO 2: NCT02277769), with concomitant topical corticosteroids (CHRONOS: NCT02260986); adolescents (≥12 to <18 y) were treated with dupilumab monotherapy every 2 weeks (200 mg for baseline weight of <60 kg; 300 mg for baseline weight of ≥60 kg) or placebo (AD ADOL: NCT03054428). RESULTS: Dupilumab showed significant rapid improvements from baseline in daily Peak Pruritus Numerical Rating Scale scores versus placebo, by day 2 in adults and day 5 in adolescents. At treatment end, dupilumab vs placebo/control had greater least-squares mean percent change from baseline in the weekly average of Peak Pruritus Numerical Rating Scale scores: SOLO -47.5% vs -20.5%; AD-ADOL -47.9% vs -19.0%; CHRONOS -57.3% vs -30.9% (P < .0001 for all). LIMITATIONS: Short duration of monotherapy trials (16 weeks). CONCLUSION: Across 4 randomized trials, dupilumab treatment showed rapid and sustained improvements in the magnitude of itch, starting with first dose; responses progressively increased and were sustained through to the end of treatment, up to 1 year.

Qualitative Assessment of Adult Patients' Perception of Atopic Dermatitis Using Natural Language Processing Analysis in a Cross-Sectional Study.

INTRODUCTION: Atopic dermatitis (AD) is an incurable, inflammatory skin disease characterized by skin barrier disruption and immune dysregulation. Although AD is considered a childhood disease, adult onset is possible, presenting with daily sleep disturbance and functional impairment associated with itch, neuropsychiatric issues (anxiety and depression), and reduced health-related quality of life. Although such aspects of adult AD disease burden have been measured through standardized assessments and based on population-level data, the understanding of the disease experienced at the patient level remains poor. This text-mining study assessed the impact of AD on the lives of adult patients as described from an experiential perspective. METHODS: Natural language processing (NLP) was applied to qualitative patient response data from two large-scale international cross-sectional surveys conducted in the USA and countries outside of the USA (non-USA; Canada, France, Germany, Italy, Spain, and the UK). Descriptive analysis was conducted on patient responses to an open-ended question on how they felt about their AD and how the disease affected their life. Character length, word count, and stop word (common words) count were evaluated; centrality analysis identified concepts that were most strongly interlinked. RESULTS: Patients with AD in all countries were most frequently impacted by itch, pain, and embarrassment across all levels of disease severity. Patients with moderate-to-severe AD were more likely than patients with mild AD to describe sleep disturbances, fatigue, and feelings of depression, anxiety, and a lack of hope that were directly associated with AD. Centrality analysis revealed sleep disturbance was strongly linked with itch. Collectively, these concepts revealed that patients with AD are impacted by both physical and emotional burdens that are intricately connected. CONCLUSIONS: Qualitative data from NLP, being more patient-centric than data from clinical standardized measures, provide a more comprehensive view of the burden of AD to inform disease management.

Treatment patterns in UK adult patients with atopic dermatitis treated with systemic immunosuppressants: data from The Health Improvement Network (THIN).

Background: There is limited understanding on patterns of systemic treatment in adults with moderate-to-severe atopic dermatitis (AD) in the UK.Objective: To characterize treatment patterns in adult AD patients prescribed immunosuppressants (IMMs) in the primary care setting.Results: Six hundred and fifty-six patients with AD (6.6%) were prescribed IMM in the analysis (mean age 52.1 years; 59.1% female; age-adjusted Charlson comorbidity index 1.4). Most prevalent (>5%) conditions at baseline were depression (10.8%), contact dermatitis (10.7%), rheumatological disease (7.9%), skin/subcutaneous tissue disorders (6.4%), upper respiratory disease (5.8%), and psoriasis (5.2%). At baseline, up to 50% of patients were prescribed ≥1 IMM. During follow-up, 42.7% of patients were prescribed oral corticosteroids (OCSs), increasing in line with IMM exposure. The most commonly prescribed IMM was methotrexate (43.3%). Ciclosporin, the only approved IMM for AD, was prescribed to 16.9% of patients.Conclusions: The prevalence of comorbidities and high rate of IMM prescriptions demonstrate the impact of AD on quality of life. The frequency of OCS prescribing in AD patients treated with IMMs suggests a lack of disease control with existing therapies, and an unmet need for safe and effective targeted agents for long-term disease control.

Dupilumab improves patient-reported symptoms of atopic dermatitis, symptoms of anxiety and depression, and health-related quality of life in moderate-to-severe atopic dermatitis: analysis of pooled data from the randomized trials SOLO 1 and SOLO 2.

Background: Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized.Objective: To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL.Methods: Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness.Results: Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 (p < .05), anxiety and depression (HADS), and QoL (DLQI) by week 2, and maintained through week 16 (p < .0001). At week 16, more dupilumab-treated than placebo-treated patients reported improvement in SCORAD itch and sleep, and no pain/discomfort (EQ-5D) (p < .0001).Limitations: Cultural differences of translated PROs.Conclusion: Dupilumab had a significant, positive impact on AD symptoms, including itch, sleep, pain, anxiety and depression, and QoL in adults with moderate-to-severe AD.

Treatment patterns of pediatric patients with atopic dermatitis: A claims data analysis.

BACKGROUND: Real-world evidence on treatment patterns of pediatric patients with atopic dermatitis (AD) is sparse. OBJECTIVE: To assess current treatment patterns in pediatric AD patients. METHODS: Retrospective observational analysis of commercial insurance and Medicaid administrative claims data (January 2011-December 2016) for pediatric AD patients, stratified by age and provider type. RESULTS: The analytic sample comprised 607,258 pediatric AD patients. Median observation period was 30.3 months. Overall, 78.6% were prescribed ≥1 AD medication; 86.7% were prescribed topical corticosteroids, and 5.4% were prescribed a calcineurin inhibitor. Systemic corticosteroids (SCSs) were prescribed for 24.4% of patients, 51.8% of whom did not have asthma or allergic comorbidities. Of the 46.6% prescribed an antihistamine and 16.2% prescribed montelukast, 62.0% and 41.3%, respectively, did not have asthma or allergic comorbidities. Systemic immunosuppressants were rarely prescribed (<0.5%). Higher potency topical corticosteroid and SCS use increased with age. Treatment patterns varied by provider type; specialists were more likely to prescribe higher potency topicals and/or systemics, regardless of patient age. A minority of patients were treated by or referred to a specialist. LIMITATIONS: Identification of AD patients relied on billing diagnoses; the disease severity was proxied by the treatment prescribed. CONCLUSION: Results indicate that SCSs, despite known risks, and other medications with disproven efficacy in AD are frequently prescribed, suggesting a need for safer and more effective alternatives.

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study.

BACKGROUND: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the long-term safety and efficacy of dupilumab in patients with AD. METHODS: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. RESULTS: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. LIMITATIONS: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. CONCLUSION: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD.

Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial.

BACKGROUND: Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator's Global Assessment 0/1 at week 16. OBJECTIVE: The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. METHODS: R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator's Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children's Dermatology Life Quality Index from baseline. RESULTS: Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5-69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9-53.3]; both p < 0.0001). Results were similar in adolescents with Investigator's Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5-66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7-48.1]; both p < 0.0001). CONCLUSIONS: Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator's Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03054428. Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4  212916 kb).