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Background Few large-scale international studies have broadly characterized the burden of atopic dermatitis (AD) across age groups among children and adolescents. Objectives To better characterize the AD burden in paediatric patients by disease severity. Methods This cross-sectional, web-based survey of paediatric patients (6 months to < 18 years old) was conducted in 18 countries representing North America, Latin America, Europe, Middle East/Eurasia and East Asia. Patients 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 or their child had eczema. AD severity was assessed using the 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 aged 6 months to < 6 years; 2898 children aged 6 to < 12 years; and 3078 adolescents aged 12 to < 18 years diagnosed with AD. Although the burden of mild AD was substantial, paediatric patients 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 those with 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 paediatric patients, especially those with moderate-to-severe disease, and suggest the need for assessments that include the impact of AD on function and daily life. [ABSTRACT FROM AUTHOR]

Introduction/Background The SCORing Atopic Dermatitis (SCORAD) index is a validated clinician-reported measurement used to assess the extent and intensity of atopic dermatitis (AD). Multiple severity threshold bands have been published to translate the SCORAD's numeric scoring index into clinically meaningful categories, most of which were developed using small patient numbers in clinical practice. Further analyses using larger patient numbers from other clinical settings may provide additional insights into AD severity and outcomes. Objective To report an analysis of SCORAD severity bands using a large, pooled dataset of global, randomized, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD. Methods Data were collected during 2013–2016 from 5 double-blind, randomized, placebo-controlled trials of dupilumab in adults with moderate-to-severe AD (NCT01859988, NCT02277743, NCT02277769, NCT02260986, NCT02755649). Total SCORAD (range 0–103) data from all patients receiving dupilumab and placebo were pooled from all visits, excluding first visit. SCORAD values were anchored to the Investigator's Global Assessment (IGA) and designated into 5 severity categories: Clear, Almost Clear, Mild, Moderate, and Severe. Spearman's rank correlations were calculated between total SCORAD and IGA values. For each integer value of SCORAD, the following were calculated to determine potential threshold bands: means analyzed with spline regression (which accounts for potential non-linear relationships between anchor and outcome, and provides a broader range of potential thresholds); medians and modes; frequencies (where the threshold of the first severity band was set to 0 and each successive severity band was set at the value of the outcome measure where the maximum anchor frequency changes category); and results of previous analyses by Chopra et al. (Br J Dermatol. 2017;177:1316-21) and Kunz et al. (Dermatology. 1997;195:10-19), modified to incorporate 5 severity categories. Thresholds for body surface area (BSA, 0–100) and total SCORAD subscales (observed SCORAD [oSCORAD, 0–83], Pruritus Visual Analog [VAS, 0–10], and Sleep Loss VAS [0–10]) by medians were also evaluated. Goodness-of-fit and concordance between bands and anchors were assessed using R2 and quadratic weighted kappa (κ)-coefficients. Results Data from 31,367 visits from 2,822 adults with moderate-to-severe AD were used. The following banding thresholds were identified using the frequencies, medians, and modes: 0–4.9 (Clear), 5–17.9 (Almost Clear), 18–36.9 (Mild), 37–68.9 (Moderate), and 69–103 (Severe; R2: 0.997; κ: 0.831). Bands identified using the means were similar: 0–5.9 (Clear), 6–17.9 (Almost Clear), 18–36.9 (Mild), 37–77.9 (Moderate), 78–103 (Severe; R2: 0.999; κ: 0.815). Severity thresholds evaluated using modified results from Chopra et al. and Kunz et al. produced the following bands, respectively: 0–5.9 (Clear), 6–24.9 (Almost Clear), 25–49.9 (Mild), 50–77.9 (Moderate), and 78–103 (Severe; R2: 0.998; κ: 0.742); and 0–9.9 (Clear), 10–28.9 (Almost Clear), 29–39.9 (Mild), 40–77.9 (Moderate), and 78–103 (Severe; R2: 0.998; κ: 0.769). Analysis of BSA and SCORAD subscales by medians produced the following bands: BSA – 0–0.09 (Clear), 1–4.9 (Almost Clear), 5–22.9 (Mild), 23–79.9 (Moderate), and 80–100 (Severe); oSCORAD - 0–4.9 (Clear), 5–15.9 (Almost Clear), 16–31.9 (Mild), 32–58.9 (Moderate), and 59–83 (Severe); Pruritus VAS - 0–1.9 (None), 2–4.9 (Mild), 5–8.9 (Moderate/Severe), and 9–10 (Very Severe); and Sleep Loss VAS - 0–0.9 (None), 1–3.9 (Mild), 4–8.9 (Moderate), and 9–10 (Severe/Very Severe). Conclusions The SCORAD threshold bands developed in this anchor-based analysis utilized a large, global, diverse data set of adult patients with AD from clinical trials and used spline regressions as a novel methodology. These potential severity bands may enhance the understanding of AD severity and disease stratification. [ABSTRACT FROM AUTHOR]

Introduction/Background Patients with atopic dermatitis (AD) have greater risk of conjunctivitis and other ocular surface disorders than the general population. In clinical trials of dupilumab in adult patients with moderate-to-severe AD, conjunctivitis and other ocular surface adverse events (AEs) were reported more frequently in patients who received dupilumab than in those who received placebo. Clinical features of ocular AEs in dupilumab-treated patients with AD are not well characterized, and there is a need for consensus on management approaches. Objectives To assess treatment and outcomes for conjunctivitis associated with dupilumab treatment for AD. Methods Treatment patterns and outcomes were assessed during a prospective observational study evaluating conjunctivitis in dupilumab-treated patients with AD (group 1) and a dupilumab-treated reference group of patients with AD without ocular symptoms (group 2). Patients were initially prescribed dupilumab by a dermatologist for treatment of AD. After at least 8 weeks, a patient was eligible to be referred to an ophthalmologist, who then determined final eligibility for the study. Dupilumab-treated patients with AD and conjunctivitis that had newly developed or significantly worsened (group 1) were followed for at least 24 weeks. A reference group of dupilumab-treated patients with AD without ocular symptoms (group 2) was evaluated at baseline visit with the ophthalmologist and Week 4. All ophthalmological treatments were at the discretion of the ophthalmologist, who also assessed conjunctivitis treatment effectiveness. Results A total of 49 patients were enrolled: 35 patients in Group 1 and 14 patients in Group 2. 3 patients in Group 2 who presented with active ocular inflammation at the initial visit were excluded from further analysis. 16 Group 1 patients (46%) and 7 Group 2 patients (64%) had a history of an ocular disorder prior to enrollment. Group 1 patients were diagnosed with AD at a younger age compared with group 2, with longer AD duration. More patients in group 1 reported history of facial AD lesions, including eyelid involvement, and history of AD facial lesions during flares. The most frequent ophthalmological diagnoses in Group 1 were non-infective conjunctivitis (46%), allergic conjunctivitis (26%) and keratoconjunctivitis (14%). The most prominent symptom was itching, followed by redness, grittiness/sandiness, swelling, tearing, burning, stinging, and light sensitivity. Corticosteroid (eye drops) were the most frequently prescribed treatment (n = 46) and their effectiveness was assessed by the ophthalmologist as excellent in 39.1% of uses and very good in 39.1%. Topical calcineurin inhibitors (either tacrolimus ointment or cyclosporin eye drops) were the next most frequently prescribed treatment (n = 31) and their effectiveness assessed as excellent in 45.2% of uses and very good in 12.9%. In participants who completed at least 24 weeks of observation, most events recovered/resolved (21/25 [84.0%]) or were resolving/recovering (3/25 [12.0%]); 1/25 [4.0%] participant had an event that was not recovered/resolved. No participants discontinued treatment with dupilumab. Conclusions Patients with AD treated with dupilumab with prolonged history of AD and facial and/or eyelid lesions may be more prone to developing ocular events. Both topical corticosteroids (eyedrops) and topical calcineurin inhibitors (eyedrops or ointment) resulted in resolution of ocular signs and symptoms and recovery in most patients, without dupilumab discontinuation. [ABSTRACT FROM AUTHOR]

Introduction/Background Seasonal trends in atopic dermatitis (AD)-related healthcare visits vary by geographical location and climate. Changes in temperature, moisture, and allergens contribute to disease fluctuation activities throughout the year. The global, placebo-controlled, 1-year LIBERTY AD CHRONOS study (NCT02260986) offers the opportunity to evaluate AD seasonality and the impact of dupilumab on moderate-to-severe AD in adults regardless of season. Objectives To identify seasonal trends in patient-reported AD severity and frequency of symptoms, and to report the effect of dupilumab treatment in adults with moderate-to-severe AD across seasons. Methods CHRONOS was a randomized, double-blind, phase 3 trial of adults with moderate-to-severe AD.1 Patients were treated with dupilumab 300 mg every week (qw), every two weeks (q2w), or placebo qw, all with concomitant topical corticosteroids (TCS). In this post hoc analysis, the proportion of patients per severity category of Patient-Oriented Eczema Measure (POEM) score (range 0–28) by month was compared between patients receiving dupilumab 300 mg q2w + TCS (n = 79) or placebo qw + TCS (n = 234) for 1 year across 10 countries in the Northern Hemisphere. Improvement in AD was determined as an increase in proportion of patients with mild and clear POEM scores (≤7). Meteorological seasons were defined as winter (December 1 – February 28/29), spring (March 1 – May 31), summer (June 1 – August 31), and fall (September 1 – November 30). Sensitivity analyses confirmed that season of enrollment was balanced across treatment arms and disease seasonality was independent of treatment length. P values are based on Chi-Square tests or Monte Carlo simulations of the Exact Test, based on sample size. All P values are nominal, and no adjustments have been made for multiple testing. Data are presented as observed. Results The proportion of patients in both treatment arms with mild and clear POEM scores (≤7) was lowest in spring months (March: 13% vs 24%; April: 10% vs 23%; May: 20% vs 44%; placebo vs dupilumab). The proportion of patients with mild and clear POEM scores was increased through summer (June: 21% vs 54%; July: 24% vs 58%; August: 29% vs 53%; placebo vs dupilumab) and fall (September: 27% vs 62%; October: 23% vs 58%; November: 21% vs 63%; placebo vs dupilumab), before beginning to decline in winter (December: 21% vs 56%; January: 16% vs 46%; February: 15% vs 41%; placebo vs dupilumab). Overall, POEM scores indicated significantly better outcomes for patients receiving dupilumab treatment vs placebo throughout the year (overall P < 0.01 for all 12 months). Conclusions Across the Northern Hemisphere, patient-reported disease severity in adults with moderate-to-severe AD was greatest in the spring months. Adults with moderate-to-severe AD receiving dupilumab treatment reported improvement in frequency of disease symptoms across all seasons compared to patients receiving placebo treatment. [ABSTRACT FROM AUTHOR]

Introduction/Background The monoclonal antibodies dupilumab (fully human) and lebrikizumab (humanized) have both demonstrated efficacy and safety in clinical trials of atopic dermatitis (AD). In the absence of direct head-to-head comparisons between dupilumab and lebrikizumab, Bucher indirect treatment comparisons (ITCs), in which treatment effects are anchored to a common comparator (e.g. placebo), provide a robust and widely accepted method of evaluating the relative efficacy of drugs, and can offer a useful framework for decision-making. Objectives To report the results of a placebo-adjusted Bucher ITC comparing maintenance of efficacy outcomes between dupilumab and lebrikizumab monotherapy at Week 52 in patients with moderate-to-severe AD who had achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75), or Investigator's Global Assessment (IGA) score 0/1 (clear/almost clear) at Week 16. Methods Placebo-adjusted Bucher ITC utilized phase 3 trial data from SOLO-CONTINUE (dupilumab; NCT02395133) and ADVOCATE 1 and 2 (lebrikizumab; NCT04146363 and NCT04178967) maintenance phase were used. Data at Week 52 was used with the following doses: 300mg dupilumab every 2 weeks (q2w) or placebo, and 250mg lebrikizumab q2w or every 4 weeks (q4w) or placebo. No adjustments were made for baseline characteristics, and missing data were imputed using non-responder imputation (NRI), excluding patients who had received topical corticosteroids during the maintenance phase of ADVOCATE 1 and 2. Outcomes included proportion of patients maintaining IGA 0/1, EASI-75, EASI-90, and 4-point improvement in peak pruritus Numerical Rating Scale score (PP-NRS ≥4) at Week 52 from SOLO-CONTINUE and ADVOCATE 1 and 2 maintenance phase baseline (Week 16). Odds ratio (OR) with 95% confidence interval (CI) are reported. Results Comparison of baseline disease characteristics indicated that the patient populations enrolled in ADVOCATE 1 and 2 maintenance phase baseline presented with lower disease severity compared with SOLO-CONTINUE, based on percentage body surface area affected. However, mean EASI and pruritus NRS baseline scores were similar in the compared trials. This analysis favored dupilumab for all outcomes evaluated at Week 52. Comparing q2w dosing, dupilumab had significantly higher ORs for EASI-75 (OR=4.15, 95%CI 1.41–12.18); EASI-90 (OR=3.72, 95%CI 1.09–12.76); IGA 0/1 (OR=4.62, 95%CI 1.02–20.92); PP-NRS ≥4 (OR=11.96, 95%CI 1.24–115.34). Compared with lebrikizumab q4w, dupilumab q2w maintained significantly higher EASI-75 OR (OR=3.53, 95%CI 1.18–10.53), while OR for the other 3 outcomes favored dupilumab, but did not reach statistical significance: EASI-90 (OR=3.31, 95%CI 0.97–11.33), IGA 0/1 (OR=3.31, 95%CI 0.73–15.08), and PP-NRS ≥4 (OR=8.79, 95%CI 0.91–84.81). Conclusions Based on a Bucher ITC utilizing data from trials with similar designs, patients treated with dupilumab q2w demonstrated higher likelihood of maintaining improvements in signs and symptoms at Week 52 compared with patients treated with lebrikizumab q2w or q4w. [ABSTRACT FROM AUTHOR]

Introduction/Background Dupilumab and lebrikizumab are both monoclonal antibodies that have demonstrated efficacy and safety in clinical trials of patients with moderate-to-severe atopic dermatitis (AD). Dupilumab targets both interleukin (IL)-4 and IL-13, and is fully human, whereas lebrikizumab selectively targets IL-13 and is humanized. However, no direct head-to-head clinical trials have been performed to compare efficacy of dupilumab vs lebrikizumab in combination with topical corticosteroids (TCS). Bucher indirect treatment comparisons (ITCs), in which treatment effects are anchored to a common comparator (e.g. placebo), provide a robust and widely accepted method of evaluating the relative efficacy of drugs in the absence of direct comparisons. Objective To report the results of a placebo-adjusted Bucher ITC of 16-week therapy for moderate-to-severe AD, comparing the efficacy of dupilumab every 2 weeks (q2w) (LIBERTY AD CHRONOS) vs lebrikizumab q2w (ADhere), in combination with TCS. Methods Placebo-adjusted Bucher ITC was conducted using published phase 3 trial data from LIBERTY AD CHRONOS (NCT02260986) and ADhere (NCT04250337). For both studies, data from the 16-week period were used, employing non-responder imputation, with the following doses: 300mg dupilumab + TCS q2w, or placebo + TCS, and 250mg lebrikizumab q2w + TCS, or placebo + TCS. No adjustments were made for baseline characteristics. Outcomes included proportion of patients achieving ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75), Investigator's Global Assessment score 0/1 (IGA-0/1; clear/almost clear), 4-point improvement from baseline in peak pruritus Numerical Rating Scale score (PP-NRS ≥4), and ≥4-point improvement from baseline in Dermatology Life Quality Index (DLQI ≥4). Odds ratio (OR) with 95% confidence interval (CI) are reported. Results Examination of baseline disease characteristics indicated that the patient populations enrolled in ADhere presented with lower disease severity compared with LIBERTY AD CHRONOS, based on IGA; however, PP-NRS, EASI, and DLQI scores were similar between both trials. This placebo-adjusted Bucher ITC favored dupilumab vs lebrikizumab with TCS combination treatment for all outcomes evaluated. Patients treated with dupilumab + TCS had a significantly higher likelihood of achieving EASI-75 (OR=2.39, 95%CI 1.10–5.19) and PP-NRS ≥4 (OR=2.63, 95%CI 1.17–5.95) at Week 16 vs those treated with lebrikizumab + TCS. OR for the endpoints IGA 0/1 and DLQI ≥4 favored dupilumab, but did not reach statistical significance: IGA 0/1 (OR=1.90, 95%CI 0.81–4.42), DLQI ≥4 (OR=2.35, 95%CI 0.94–5.87). Conclusion A placebo-anchored Bucher ITC approach showed that the likelihood of achieving improvements in signs, symptoms, and quality of life is higher for patients treated with dupilumab + TCS vs lebrikizumab + TCS. [ABSTRACT FROM AUTHOR]