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Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P =.003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. Short-term, 16-week treatment period. Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s13555-023-01061-4.Publisher Correction to: Dermatol Ther (Heidelb) (2024) 14:261–270https://doi.org/10.1007/s13555-023-01061-4The infographic was missing from this article and should have appeared as below.InfographicGraphThe original article has been corrected.By Eric L. Simpson; Ben Lockshin; Lara Wine Lee; Zhen Chen; Moataz Daoud and Andrew KorotzerReported by Author; Author; Author; Author; Author; Author [Extracted from the article]

[Display omitted] 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. This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab. 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. 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 T H 17-cell subsets (day 14), and increased expression of genes relevant for IL-17, neutrophil, and complement pathways (day 7) were also observed. 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 T H 17 cells, neutrophils, and complement activation as potential mechanisms to explain these findings. [ABSTRACT FROM AUTHOR]

Introduction/Background While previous studies into continuous long-term dupilumab treatment for adults with moderate-to-severe atopic dermatitis (AD) demonstrated sustained efficacy, further study into long-term safety and efficacy data regarding dupilumab in children is needed. Objectives To evaluate the impact of treatment with dupilumab and low-potency topical corticosteroids (TCS) for up to 2 years on efficacy and safety measures in children aged 6 months to 5 years with moderate-to-severe AD. Methods Children aged 6 months to 5 years with moderate-to-severe AD, who had participated in prior dupilumab pediatric AD studies were enrolled in a phase 3 open label extension (OLE) study. Patients received subcutaneous dupilumab every 4 weeks; 200 mg for children weighing 5 to <15 kg, 300mg for 15 to <30 kg. Topical AD treatments were allowed. Efficacy outcomes assessed include the proportion of patients who achieved 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) score and the proportion of patients who achieved an Investigator Global Assessment (IGA) score of 0/1 as observed from OLE baseline to 2 years. Safety was also evaluated. Results A total of 180 patients were included in the 6 month to 5 years cohort; mean (±SD) age at OLE baseline was 3.9 (1.3) years with mean (SD) duration of AD of 3.5 (1.3) years. At OLE baseline, 29.4% of patients achieved EASI-75, improving to 85.1% at 52 weeks and 92.1% at 104 weeks. Similarly, 12.8% of patients achieved IGA 0/1 at OLE baseline, improving to 36.0% at Week 52 and 40.6% at Week 104. Total treatment-emergent adverse events (TEAEs) were observed in 87.8% of patients (intensity: mild 24.4%, moderate 52.2%, severe 11.1%). TEAEs assessed as related to dupilumab by the study investigators were reported in 18.3% of patients; the most prevalent were conjunctivitis (2.8%), allergic conjunctivitis (1.7%), nasopharyngitis (1.7%) and urticaria (1.7%). Serious TEAEs assessed as related to dupilumab by the study investigators were observed in 0.6% of patients. Conclusions Treatment with dupilumab for up to 2 years in young children with moderate-to-severe AD demonstrated efficacy outcomes, with sustained improvement in clinical signs reported in a large proportion of patients. Results are consistent with the known safety profile for dupilumab. [ABSTRACT FROM AUTHOR]

Introduction/Background Patients with atopic dermatitis (AD) have an increased risk of cutaneous, extracutaneous, and systemic infections with a considerable associated cost burden. Certain treatments used to manage AD, such as immunosuppressants and Janus kinase inhibitors, can increase the risk of infection. Data from the LIBERTY AD open-label extension study (OLE; NCT01949311) indicate that continuous dupilumab treatment for up to 4 years in adults with moderate-to-severe AD is not associated with an increased risk of overall systemic or cutaneous infections.1 Objectives To report exposure-adjusted incidence rates (EAIR) of infections in adults with moderate-to-severe AD treated with dupilumab for up to 5 years. Methods The OLE was a phase 3, multicenter, open-label extension trial that enrolled adults with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1–3). During the OLE, patients were treated with 300mg dupilumab weekly (qw). 226 patients transitioned to 300mg every 2 weeks starting from Week 108 to align with approved dosage. Concomitant topical treatments for AD were permitted. The EAIR (patients with ≥1 event/100 patient-years [nP/100PY]) was calculated for treatment-emergent infections (Medical Dictionary for Regulatory Activities [MedDRA] System Organ Class [SOC] infections and infestations) and skin infections for the overall study population (N=2,677). Skin infections were defined as adjudicated non-herpetic skin infections from the SOC infections and infestations plus, conservatively, all MedDRA Preferred Terms (PT) in MedDRA High Level Term herpes viral infections. Because the OLE lacked a control arm, infection data from adults with moderate-to-severe AD receiving placebo qw + topical corticosteroids (TCS) in the 1-year LIBERTY AD CHRONOS trial (NCT02260986; n=315) are included for comparison. Data are presented as observed. Results From the 2,677 patients enrolled, 2,207/557/334 completed treatment up to Week 52/148/260. The most common reasons for study withdrawal during the OLE were dupilumab approval and commercialization (810/1,380 patients; 58.7% of withdrawals) and patient withdrawal (248/1,380 [18.0%]). Treatment-emergent adverse events led to permanent discontinuation in 101 (3.8%) patients. The EAIR of patients with ≥1 treatment-emergent infection was lower in this OLE vs the placebo qw + TCS arm of the 1-year CHRONOS trial (70.7 vs 107.0 nP/100PY). Over this 5-year OLE, 50 patients (0.9 nP/100PY) had ≥1 serious infection, 53 (0.9 nP/100PY) had ≥1 severe infection, and 20 (0.3 nP/100PY) experienced ≥1 infection resulting in permanent treatment discontinuation. Skin infections were reported in 535 patients (11.0 nP/100PY), comprising non-herpetic skin infections (249 patients; 4.6 nP/100 PY) and herpes viral infections (343 patients; 6.6 nP/100 PY). The EAIR of skin infections decreased throughout the OLE (1 year: 17.2 nP/100 PY; 3 years: 11.9 nP/100 PY; 5 years: 11.0 nP/100 PY) and was lower than the CHRONOS placebo qw + TCS arm (29.5 nP/100 PY). The most common PTs (≥5.0 nP/100PY) from the SOC infections and infestations were nasopharyngitis (774 patients; 17.6 nP/100PY), upper respiratory tract infection (365 patients; 7.0 nP/100PY), and conjunctivitis (277 patients; 5.2 nP/100PY; representing conjunctivitis of unspecified or undetermined etiology, including non-infectious cases). Conjunctivitis was the most common infection PT leading to treatment discontinuation (10 patients; 0.2 nP/100PY). The EAIR of serious infections remained stable during the OLE (1 year: 0.8 nP/100PY; 3 years: 0.9 nP/100PY; 5 years: 0.9 nP/100PY). Conclusions Long-term dupilumab treatment in adults with moderate-to-severe AD does not increase risk of systemic or cutaneous infections. Rates of treatment-emergent infections, including skin infections, in the OLE for up to 5 years were low, compared with patients receiving placebo + TCS in a 1-year study. Serious infection rates remained low and stable over the 5-year OLE. This report reinforces the known long-term safety profile of dupilumab from an infection perspective. [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 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 Pruritus is one of the essential features of atopic dermatitis (AD) and is consistently reported by patients as the most burdensome symptom of the disease. Itch not only impacts quality of life but also contributes to furthering AD pathogenesis through the itch-scratch cycle and additional breakdown of the epidermal barrier. A treat-to-target concept established goals to guide treatment with systemic therapies in AD, including those for itch.1-3 Objectives To assess onset and maintenance of optimal itch response according to the treat-to-target concept in adult patients with moderate-to-severe AD treated with dupilumab + concomitant topical corticosteroids (TCS). Methods LIBERTY AD CHRONOS (NCT02260986), a 52-week trial, enrolled patients aged ≥18 years with moderate-to-severe AD. Patients treated with dupilumab every 2 weeks + TCS or placebo + TCS were included in this post hoc analysis. Optimal itch response per the treat-to-target concept was defined as Peak Pruritus Numerical Rating Scale (PP-NRS) score of ≤4, achieved after 6 months of treatment1. We assessed time to optimal itch response, percentage of patients achieving optimal itch response, and maintenance of optimal itch response. For maintenance of optimal itch response, the total number and percentage of weeks with PP-NRS ≤4 were calculated for each patient, and maximum duration was assessed as the longest period of consecutive weeks with PP-NRS ≤4 for each patient. Results Median (interquartile range) PP-NRS score at baseline was 7.7 (6.6–8.5) for patients treated with dupilumab + TCS and 7.6 (6.3–8.6) for patients who received placebo + TCS. Median time (95% CI) to achieve optimal itch response was 29 (22–43) days for patients treated with dupilumab+ TCS and 64 (43–105) days for patients who received placebo + TCS (HR [95% CI] = 1.668 [1.292–2.153]; P < 0.0001). 61.3% of patients treated with dupilumab + TCS achieved optimal itch response at 6 months, compared with 26.7% of those who received placebo + TCS (P < 0.0001). Significantly more patients treated with dupilumab + TCS maintained optimal itch response than patients who received placebo + TCS through 52 weeks. In the dupilumab group, median (Q1–Q3) maintenance of optimal itch response was 40 (11–50) weeks, compared with 3 (0–23) weeks in the placebo group (P < 0.0001), which corresponds to 77.1% of the total study duration (52 weeks) in the dupilumab group, compared with 5.7% in the placebo group. Maximum consecutive duration with optimal itch response was also significantly longer in dupilumab-treated patients than in patients who received placebo (median [Q1–Q3]: 29.2 [4–50] weeks for dupilumab vs 2.0 [0–13] weeks for placebo; P < 0.0001). Conclusions Patients treated with dupilumab + TCS achieved optimal itch response rapidly and significantly faster than patients who received placebo + TCS; 29 days in dupilumab-treated patients compared with 64 days in those who received placebo. Significantly more patients treated with dupilumab + TCS achieved and maintained optimal itch response than patients who received placebo + TCS through 52 weeks. Dupilumab + TCS also led to a significantly longer maintenance of optimal itch response (40 weeks) compared with placebo + TCS (3 weeks). [ABSTRACT FROM AUTHOR]

P-values shown are for comparison of proportions of patients who achieved CDLQI scores of 0 or 1 (indicating no effect on their quality of life) at Wk 16 between dupilumab-treated and placebo-treated arms. Plain language summary available online Author Video: https://youtu.be/Bq1a6Owymks https://doi.org/10.1093/bjd/ljad124 Dear editor, Severe atopic dermatitis (AD) in children poses a high disease burden and requires long-term management, which in turn relies on monitoring symptoms and quality of life (QoL) over time. Dupilumab improves patient-reported symptoms and health-related quality of life in children aged 6-11 years with severe atopic dermatitis. [Extracted from the article]

The pharmacokinetics (PKs) and exposure–efficacy of dupilumab have not been fully described for adults with atopic dermatitis (AD). Our objectives were to analyze the PKs and exposure–efficacy of dupilumab in adults with AD and compare the results of Japanese and overall populations. Adults with moderate‐to‐severe AD were randomly assigned to dupilumab (300 mg weekly [qw] or every 2 weeks [q2w], 200 mg q2w, 300 mg every 4 weeks [q4w], or 100 mg q4w) or placebo for 16 weeks in a randomized, double‐blind, placebo‐controlled, dose‐ranging phase IIb trial (NCT01859988). This analysis included 379 patients (58 Japanese). Functional dupilumab concentrations increased in a dose‐dependent manner; at lower concentrations, increases were greater than dose‐proportional because of nonlinear, target‐mediated clearance. Dupilumab pharmacokinetics were comparable in Japanese and non‐Japanese patients with similar body weights. Week 16 efficacy parameters, including Investigator's Global Assessment score 0/1, greater than or equal to 75% reduction from baseline in the Eczema Area and Severity Index (EASI), and percentage change from baseline in EASI and pruritus Numerical Rating Scale, generally increased with week 16 trough concentration; the plateau of these exposure–efficacy relationships occurred for most patients at exposures associated with the 300 mg q2w and 300 mg qw regimens. Japanese ethnicity did not remain in the population PK model as covariate with or without accounting for body weight differences. In Japanese and non‐Japanese patients, efficacy responses increased with week 16 dupilumab trough concentrations in a similar manner. Dupilumab 300 mg qw and q2w regimens were recommended for further evaluation in larger phase III studies. [ABSTRACT FROM AUTHOR]

Introduction/Background Dupilumab has previously shown overall efficacy in treating atopic hand and foot dermatitis. Objective To report the effect of dupilumab treatment on individual signs of atopic hand and foot dermatitis. Methods: The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged =12 years with moderate-to-severe (Investigator's Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis presents the proportion of patients reporting absent, mild, moderate, or severe erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures, assessed by the modified total lesion sign score (mTLSS) in hands and feet. Results: At baseline, most patients had scores of moderate or severe signs on their hands. Of the 133 patients enrolled, over 65% of patients treated with dupilumab (n = 67) achieved an absent or mild score by Week 16 in each of the signs/symptoms assessed. Proportion of patients with absent or mild hand scores increased from baseline to Week 16 in erythema (9% vs 71.6%), scaling/flaking (16.4% vs 74.7%), lichenification (4.5% vs 65.6%), vesiculation/erosion (43.3% vs 89.6%), edema (44.7% vs 86.6%), and fissures (23.9% vs 83.5%). Proportion of patients with absent or mild foot scores increased from baseline to Week 16 in erythema (56.7% vs 80.6%), scaling/flaking (56.7% vs 82.1%), lichenification (53.8% vs 82.1%), vesiculation/erosion (76.1% vs 86.6%), edema (76.1% vs 88.1%), and fissures (77.6% vs 86.6%). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions: Dupilumab treatment in patients improves signs of hand and foot dermatitis, including erythema, scaling/flaking, lichenification, vesiculation/erosion, edema, and fissures. [ABSTRACT FROM AUTHOR]

Introduction/Background As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point. Objective To evaluate the proportion of pediatric patients achieving and maintaining mild or no itch (defined by a SCORing Atopic Dermatitis (SCORAD) itch visual analog scale (VAS; 0-10 over last 3 days) score of lower than 4) across 5 visits during a 52-week open label extension trial of dupilumab. Methods: Patients who previously participated in 16-week trials and were aged 0.5-5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6-11 years (LIBERTY AD PEDs; NCT03345914), and 12-17 years (LIBERTY AD ADOL; NCT03054428), were subsequently enrolled in the phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300 mg q4w or 200/300 mg q2w (body weight <60 or ≥60 kg, respectively). In this analysis, patients with a SCORAD itch VAS score of greater than 4 at OLE baseline, were assessed for the maintenance of SCORAD itch VAS lower than 4, at 5 timepoints: Weeks 4, 16, 28, 40, and 52. Results: In 763 patients, 400 patients with a SCORAD itch VAS score of greater than 4 were assessed. Mild or no itch was achieved in at least 4 of 5 timepoints in most patients aged 0.5-5 years (55/110; 50%), 6-11 years (76/148; 51%), and 12-17 years (73/142; 51%). Across these age groups, over 65% maintained this response for at least 3 of 5 timepoints. Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions: Most pediatric patients achieved improvement in itch, maintained during 1 year of treatment with dupilumab. Results were consistent for infants/preschoolers, children, and adolescents. [ABSTRACT FROM AUTHOR]

Background Dupilumab has shown efficacy in the treatment of atopic dermatitis (AD) in clinical trials, but there is a need for longterm data on patients starting dupilumab treatment for atopic dermatitis in a real-world setting. Methods: PROSE (NCT03428646) is an ongoing 5-year, prospective, observational study of patients aged ≥12 years who initiated commercially available dupilumab treatment for AD per country-specific prescribing information. Patients received a loading dose of dupilumab at baseline, without restrictions on post-baseline dosing changes or concomitant medication and were encouraged to stay in the study if they discontinued dupilumab. Data presented are descriptive, from a 3-year interim analysis. Results: 857 patients were enrolled. In these patients, mean (SD) age was 40.1 (17.9) years, AD duration 17.4 (16.2) years, and dupilumab treatment duration 23.1 (13.7) months (M). Mean (SE) baseline EASI total score was 16.2 (0.4), Pruritus Numerical Rating Scale (NRS) 7.1(0.1), Dermatology Life Quality Index (DLQI) 13.3 (0.3), and skin pain NRS 5.4 (0.1). 189 (22.1%) patients had withdrawn by data cut-off; the most common reasons for discontinuation were withdrawal of consent in 76 patients and loss to follow-up in 30. Mean (SE) EASI total score was 5.6 (0.4) at 3M, 2.9 (0.2) at 12M, 2.7 (0.4) at 24M, and 1.7 (0.3) at 36M. Mean (SE) change from baseline in Peak Pruritus NRS was -3.5 (0.2) at 3M, -4.2 (0.2) at 12M, -4.7 (0.2) at 24M, and -5.1 (0.3) at 36M. Mean (SE) change from baseline in DLQI was -7.4 (0.3) at 3M, -8.3 (0.7) at 12M, -9.2 (0.9) at 24M, and -8.8 (1.5) at 36M. Mean (SE) change from baseline in skin pain NRS was -3.3 (0.3) at 3M, -3.8 (0.2) at 12M, -4.0 (0.3) at 24M, and -4.6 (0.3) at 36M. Safety findings were consistent with the previously described safety profile of dupilumab. Conclusion: In this interim analysis of the PROSE registry, sustained disease control was observed in patients with moderate-to-severe AD for up to 3 years after initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] =16; body surface area =10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) =3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] =4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods: Skin clearance was assessed by EASI, with response defined as an improvement =75% (EASI75), =90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (=4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a posthoc analysis. Results: EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P<0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P<0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P<0.001), with greater improvement observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P<0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P<0.001), with greater proportions observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P<0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P<0.001) and at week 1 (nominal P<0.001). Conclusions: Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement. [ABSTRACT FROM AUTHOR]

Background Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, and dupilumab, an anti-interleukin 4 receptor a monoclonal antibody, have been approved for the treatment of patients with moderate-to-severe atopic dermatitis (AD). The efficacy of abrocitinib and dupilumab as monotherapy or in combination with medicated topical therapy has been demonstrated in multiple phase 3 clinical trials. As is the case with many therapies, some patients with AD may need to discontinue treatment with dupilumab (due to inadequate efficacy, intolerable side-effects, patient choice, or other reasons) and switch to other systemic therapies. Objective To evaluate the long-term treatment response in patients with moderate-to-severe AD who switched from dupilumab to abrocitinib, as it is valuable information for prescribers and patients to consider when making treatment decisions. Methods: The phase 3 JADE COMPARE trial (NCT03720470) evaluated the efficacy of abrocitinib (100 mg or 200 mg once daily) and dupilumab (300 mg every 2 weeks) versus placebo in combination with topical medicated therapy in patients with moderate-to-severe AD through week 16. After a wash-out period, dupilumab-treated patients from JADE COMPARE who enrolled in the ongoing long-term extension trial JADE EXTEND (NCT03422822; clinical data cutoff: Sept 25, 2021) were randomised to receive double-blinded treatment with abrocitinib 100 mg or 200 mg. This post hoc analysis evaluated the response to dupilumab through week 16 in JADE COMPARE and thereafter in JADE EXTEND following a switch to abrocitinib through week 104 of total treatment duration/week 84 of abrocitinib treatment. Assessments included Investigator's Global Assessment score of 0 (clear) or 1 (almost clear) with a =2-point improvement from baseline (IGA 0/1), =75% or =90% improvement from baseline in Eczema Area and Severity Index (EASI-75 or EASI-90), =4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS4; PP-NRS used with permission from Regeneron Pharmaceuticals, Inc., and Sanofi), and a PP-NRS score of 0 or 1 (PP-NRS 0/1). JADE EXTEND data are presented as observed; patients with missing data at a visit were excluded. Analyses included both dupilumab responders and non-responders. Results: Overall, 242 patients were treated with dupilumab in JADE COMPARE (mean age: 37 years; IGA score 4: 33%). Of those, 203 enrolled in JADE EXTEND and received abrocitinib 200 mg (n=73) or abrocitinib 100 mg (n=130). After 16 weeks of treatment with dupilumab in JADE COMPARE, the proportion of responders was 39% for IGA 0/1, 66% for EASI-75, 39% for EASI-90, 57% for PP-NRS4, and 24% for PP-NRS 0/1. As early as 2 weeks after switching to abrocitinib (200 mg/100 mg) in JADE EXTEND, the proportion of responders was observed to increase in a dose-dependent manner, respectively, for IGA 0/1 (61%; 51%), EASI-75 (90%; 85%), EASI-90 (60%; 54%), PP-NRS4 (81%; 72%), and PP-NRS 0/1 (47%; 37%). Long-term efficacy was observed out to week 84 (Figure). Conclusions: In patients with moderate-to-severe AD who received prior treatment with dupilumab, switching to abrocitinib resulted in dose-dependent increases in the proportion of responders as early as week 2 after treatment with abrocitinib. This efficacy continued to be observed long-term through week 84 of abrocitinib treatment. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep disturbances. Currently, dupilumab is the only systemic therapy and biologic medication approved by the United States Food and Drug Administration for moderate-to-severe AD in adults and children. There is a sparsity of literature available on determining treatment failure with dupilumab and the next steps health care providers can take to treat AD. Individual goals and quality of life and not just body surface area should be considered when defining treatment failure. Possible confounding dermatoses also should be ruled out. Early identification of dupilumab-induced adverse events is important. For most patients, dupilumab can be continued while treatment for the adverse event is initiated. Adjusting the frequency of dupilumab dosing also may be considered in some circumstances. Adjuvant therapies, such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, or phototherapy can be added but the safety and efficacy of these combination treatments are not known at this time. [ABSTRACT FROM AUTHOR]

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a realworld setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebocontrolled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double‐blind, placebo‐controlled, parallel‐group, phase III trials in adolescents (12–17 years; LIBERTY AD ADOL) and children (6–11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure‐response (E‐R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate‐to‐severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non‐weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E‐R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment‐emergent conjunctivitis. Based on these analyses, a weight‐tiered posology was proposed for adolescents (200/300 mg q2w in patients 30–< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15–< 30 kg, 200 mg q2w in patients 30–< 60 kg) with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Introduction/Background Dupilumab has previously shown to significantly improve signs, symptoms, and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis. Objective To investigate the efficacy of dupilumab across morphological subtypes in patients with moderate-to-severe atopic hand and foot dermatitis. Methods: The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged =12 years with moderate-to-severe (Investigator's Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis reports the percent change from baseline in modified total lesion sign score (mTLSS) by hand and foot morphological subtypes: chronic dry fissured, hyperkeratotic (palmar/plantar), and other. Results: 133 patients enrolled into this study and were randomized to dupilumab (n = 67) or placebo (n = 66). Atopic hand and foot morphologies were reported in 3 categories: chronic dry fissured (n = 63), hyperkeratotic (palmar/plantar; n = 37), and other (n = 33) In the "other" category, dyshidrotic was the most frequent morphology (n = 13). mTLSS values were similar at baseline for all morphological subtypes. At Week 16, greater improvements were seen in the percent change from baseline (SE) in mTLSS for patients receiving dupilumab vs placebo in all categories: chronic dry fissured (-65.6% [5.1] vs -31.5% [6.2]), hyperkeratotic (palmar/plantar; -58.2% [7.6] vs -11.8% [7.7]), and other (-64.5% [11.6] vs -29.9% [9.0]). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis. Conclusions: The efficacy of dupilumab remains consistent across different hand and foot dermatitis morphologies and shows higher treatment benefit across subtypes compared with placebo. [ABSTRACT FROM AUTHOR]

Background: Laboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring. Objective: The aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial. Methods: Adolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters. Results: Of 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant. Conclusion: No clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment. Trial Registration: ClinicalTrials.gov: NCT03054428. 6vz_jLtTkCJ6tzGx5HdiGv Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB) [ABSTRACT FROM AUTHOR]

Background: Conjunctivitis is a known comorbidity of atopic dermatitis. Dupilumab clinical trials for moderate-to-severe atopic dermatitis in adults showed a higher conjunctivitis incidence for dupilumab-treated patients than placebo-treated patients, whereas trials for uncontrolled asthma reported lower rates for both dupilumab and placebo. Objective: The objective of this study was to evaluate the incidence and severity of conjunctivitis in dupilumab clinical trials in adolescents with moderate-to-severe atopic dermatitis or uncontrolled asthma. Methods: We evaluated the incidence of conjunctivitis in adolescents (aged 12 to < 18 years) in three phase III trials. Ocular events were diagnosed and treated based on patient-reported symptoms and an external eye examination by study investigators, in most cases without an ophthalmologic referral. In LIBERTY AD ADOL (16-week, randomized, placebo-controlled, double-blinded trial), adolescents with moderate-to-severe atopic dermatitis were randomized to subcutaneous placebo, dupilumab 300 mg every 4 weeks, or dupilumab every 2 weeks (200 mg, patients < 60 kg at baseline; 300 mg, ≥ 60 kg at baseline). In LIBERTY AD PED-OLE (open-label extension), pediatric patients from previous dupilumab atopic dermatitis trials received dupilumab 2 mg/kg or 4 mg/kg weekly (up to 300 mg) or 300 mg every 4 weeks. In LIBERTY ASTHMA QUEST (randomized, double-blinded, placebo-controlled trial), patients with uncontrolled moderate-to-severe asthma were randomized to 52 weeks of add-on therapy with dupilumab 200 or 300 mg every 2 weeks or matched-volume placebo. Results: In ADOL, more dupilumab-treated (17/165; 10.3%) than placebo-treated patients (4/85; 4.7%) reported one or more conjunctivitis event. All events were mild to moderate in severity; 12 (7.3%) dupilumab-treated and 4 (4.7%) placebo-treated patients received treatment. Most patients with conjunctivitis (dupilumab, 12/17; placebo, 4/4) recovered/resolved during the treatment period. The risk of conjunctivitis showed no relationship with dupilumab serum concentration. In PED-OLE, 12/275 adolescents (4.4%) reported one or more conjunctivitis event. Most conjunctivitis events were mild to moderate. Ten patients received treatment for conjunctivitis. Ten patients recovered/resolved during the study. In QUEST, similar low proportions of dupilumab-treated (2/68, 2.9%) and placebo-treated (1/39, 2.6%) adolescents reported one or more conjunctivitis event. All events were mild to moderate. One dupilumab-treated patient received treatment for conjunctivitis. All cases recovered/resolved during the study. No patients in these trials discontinued study treatment temporarily or permanently because of conjunctivitis. In ADOL, one case of unspecified viral keratitis (specific viral etiology not known) in the dupilumab 300-mg every 4 weeks group and one case of allergic blepharitis in the placebo group were reported; both events resolved during the treatment period, and neither led to treatment discontinuation. Conclusions: Dupilumab-treated adolescents in atopic dermatitis trials had a higher incidence of conjunctivitis than placebo-treated patients, whereas overall rates of conjunctivitis among adolescents in the asthma trial were lower than in atopic dermatitis trials and were similar for dupilumab- and placebo-treated patients. Most events were mild to moderate, most recovered/resolved, and none prompted study withdrawal. These results are similar to those reported in adult trials and support a drug–disease interaction. ClinicalTrials.gov Identifiers: NCT03054428, NCT02612454, NCT02414854. FSZJ5YMfe98kiNB8ymgqFL Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma (MP4 18453 kb) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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) [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) of the hands and/or feet is often chronic, difficult to treat and substantially impacts patient quality of life. This study aims to report the effect of dupilumab treatment on signs, symptoms and quality of life in patients with atopic hand and foot dermatitis using dedicated clinical and patient reported instruments. The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients ≥12 years with moderate-to-severe [Investigator's Global Assessment (IGA) 3/4] atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg q2w in adults; 200/300 mg every 2 weeks in adolescents, or placebo for 16 weeks. The primary endpoint was hand and foot IGA 0/1 score at Week 16. Safety/tolerability was assessed. The 133 patients enrolled were randomized to dupilumab (n = 67) or placebo (n = 66). At Week 16, the primary and all secondary endpoints were met. Significantly more patients in the dupilumab vs. placebo group achieved hand and foot IGA 0/1 (40.3% vs. 16.7%; P = 0.003; primary endpoint) and ≥4-point improvement in the hand and foot Peak Pruritus Numerical Rating Scale (52.2% vs. 13.6%; P < 0.0001; a key secondary endpoint). Dupilumab-treated patients experienced significant improvement in percent change from baseline in the modified Total Lesion Sign Score for hand and foot lesions vs. placebo [LS mean (SE) −69.4 (5.8) vs. −31.0 (5.9); P < 0.0001] and Hand Eczema Severity Index [HECSI; LS mean (SE) −74.8 (6.3) vs. −39.9 (6.2); P < 0.0001]. At Week 16, treatment with dupilumab also significantly increased the proportion of patients achieving a 75% improvement in HECSI (46.9% vs. 21.5%; P = 0.0028) and improved Quality of Life in Hand Eczema Questionnaire scores [LS mean (SE) −40.3 (4.0) vs. −16.2 (4.2); P < 0.0001]. The most common TEAEs (≥10%) were nasopharyngitis (16% vs. 11%) and dermatitis atopic (5% vs. 18%). Dupilumab significantly improved signs, symptoms and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis and had an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, had a superior efficacy vs. dupilumab in head-to-head randomized trials in moderate-to-severe atopic dermatitis (AD). Data on patients who switched from dupilumab to abrocitinib have been limited. To evaluate abrocitinib response in patients with moderate-to-severe AD who were responders or nonresponders to dupilumab. Dupilumab-treated patients from the JADE DARE trial (NCT04345367), which was designed to compare the efficacy and safety of 26-week abrocitinib (200 mg daily) vs. dupilumab (300 mg bi-weekly) in patients receiving topical medicated therapy, had the option to switch to abrocitinib 200 mg by enrolling to an open-label JADE EXTEND trial (NCT03422822). In this analysis, we evaluated the response to abrocitinib 200 mg at week 12 of JADE EXTEND of responders and nonresponders to dupilumab at week 26 of JADE DARE. Response and nonresponse were defined as patients’ achievement and nonachievement, respectively, of ≥50%, ≥ 75% or ≥90% improvement from the JADE DARE baseline in Eczema Area and Severity Index (EASI-50, EASI-75 or EASI-90), ≥ 4-point improvement from JADE DARE baseline in Peak Pruritus Numerical Rating Scale (PP-NRS4), and PP-NRS score of 0 or 1 (PP-NRS 0/1) at week 26 of JADE DARE. In addition, changes in individ - ual EASI and PP-NRS scores were evaluated in dupilumab-treated patients with significant skin lesions (EASI ≥16) or itch burden (PP-NRS ≥7) at week 26 of JADE DARE. Patients who withdrew from JADE EXTEND were considered nonresponders after withdrawal. Additionally, adverse events (AEs) of dupilumab-treated patients from JADE DARE occurring during JADE EXTEND were assessed. Out of 365 dupilumab-treated patients in JADE DARE, 312 received treatment in JADE EXTEND. After 12 weeks of switching to abrocitinib, EASI-50 response was maintained in 98% of patients (277/282) who had attained EASI-50 after 26 weeks of dupilumab. Those values were 95% (232/245) for EASI-75, 88% (143/162) for EASI-90, 91% (192/210) for PP-NRS4 and 79% (86/109) for PP-NRS 0/1. Conversely, among patients who did not attain EASI-50 after 26 weeks of dupilumab, switching to abrocitinib for 12 weeks resulted in 75% (12/16) of patients attaining this level of response. Those values were 77% (41/53) for EASI-75, 62% (85/136) for EASI-90, 51% (46/90) for PP-NRS4 and 45% (86/192) for PP-NRS 0/1. Among dupilumab-treated patients with EASI ≥16 at week 26 of JADE DARE, 91% (10/11) experienced improvements (i.e. EASI <16), after switching to abrocitinib for 12 weeks; in two such patients, score changes were consistent with ≥97% improvement in EASI from JADE DARE week 26 to JADE EXTEND week 12 (from 45.5 to 0 and from 42.3 to 1.4). Among patients with PP-NRS ≥7 at JADE DARE week 26, 75% (12/16) showed an improvement (i.e. PP-NRS score <7), 12 weeks after switching to abrocitinib; three such patients achieved a PP-NRS score of 0 or 1. During JADE EXTEND, 57% (178/312) of patients who previously received dupilumab experienced AEs and 3% (9/312) experienced serious AEs. Most patients with moderate-to-severe AD who switched from dupilumab to abrocitinib after 26 weeks maintained their response, while a great proportion of the nonresponders achieved clinically relevant efficacy outcomes 12 weeks after the switch. The safety profile of abrocitinib after switching from dupilumab was consistent with that of previous safety analyses; serious AEs were relatively rare. [ABSTRACT FROM AUTHOR]

Background: Patients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. Objective: The aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD. Methods: This analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates. Results: Of 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p < 0.05), as were bacterial and other non-herpetic skin infections (risk ratio 0.44; p < 0.001). Although herpesviral infection rates overall were slightly higher with dupilumab than placebo, clinically important herpesviral infections (eczema herpeticum, herpes zoster) were less common with dupilumab (risk ratio 0.31; p < 0.01). Systemic anti-infective medication use was lower with dupilumab. Conclusions: Dupilumab is associated with reduced risk of serious/severe infections and non-herpetic skin infections and does not increase overall infection rates versus placebo in patients with moderate-to-severe AD. ClinicalTrials.gov Identifiers: NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649. [ABSTRACT FROM AUTHOR]

• In this pooled analysis dupilumab significantly improved signs and symptoms of AD. • Dupilumab treatment alleviated pain/discomfort on the EuroQoL-5D. • Patient distribution within responder categories improved over time with dupilumab. • No new safety signals were observed with dupilumab. • Dupilumab had an overall favorable benefit-risk profile. Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety. A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo. Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–<90%/≥50–<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1–3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo. Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background and purpose: There is a need for new treatment options for moderate-to-severe atopic dermatitis (AD) in adults. Dupilumab, a fully human anti-interleukin-4 receptor a monoclonal antibody, has recently been approved for this indication. Methods: A pooled analysis of a phase 2a (NCT01548404) and a phase 2b (NCT01859988) study and a subanalysis of the 2b study evaluated the efficacy and safety of subcutaneous dupilumab 300 mg once weekly (qw) and every 2 weeks (q2w) in adults with moderate-to-severe AD. Results: Dupilumab significantly improved clinical outcomes in both analyses at week 12. Itch was significantly improved in the pooled analysis as measured by peak pruritus Numerical Rating Scale, 5-dimension pruritus scale, and SCORing Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) pruritus scores (all p < .0001 vs. placebo at week 12). Sleep loss was significantly improved (SCORAD VAS sleep loss score; p < .0001 vs. placebo at week 12); similar results were shown for the q2w dose. Dupilumab had an acceptable safety profile. Conclusions: Consistent with previous studies, dupilumab qw and q2w significantly improved signs and symptoms of AD at week 12, including improvements in itch and sleep loss. Implications for practice: Subcutaneous dupilumab is an effective new treatment option for adults with moderateto- severe AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a type 2 inflammatory disease characterized by elevations in several biomarkers including serum IgE—a key downstream mediator in the type 2 adaptive immune response. Patients with moderate-to-severe AD were enrolled for 16 weeks in any of six randomized, placebo-controlled, phase 3 studies: in LIBERTY AD PRESCHOOL, (NCT03346434 part B) patients aged 6 months to 5 years were treated with dupilumab 200/300 mg every 4 weeks (q4w) + topical corticosteroids (TCS; n = 83) or placebo + TCS (n = 79); in LIBERTY AD PEDS (NCT03345914), patients aged 6–11 years were treated with dupilumab + TCS [100/200 mg q2w (n = 122), 300 mg q4w (n = 122)] or placebo + TCS (n = 123); in LIBERTY AD ADOL (NCT03054428), patients aged 12–17 years were treated with dupilumab [200/300 mg q2w (n = 82), 300 mg q4w (n = 83)] or placebo (n = 85); and in LIBERTY AD CHRONOS/SOLO1/SOLO2 (NCT02260986/NCT02277743/NCT02277769, pooled), patients aged ≥18 years were treated with dupilumab [300 mg q2w (n = 563),300 mg qw (n = 781) ] or placebo (n = 775). The TCS were allowed in CHRONOS only. At Week 16, dupilumab treatment significantly (P < 0.0001) reduced median total serum IgE levels [kU/L (IQR)] compared with placebo in patients aged 6 months to 5 years [843 (207–3300) vs. 3625 (540.5–8585)], 6–11 years [1519 (532–3808) vs. 3862 (1166–9999)], 12–17 years [1391 (436–2842) vs. 4569 (800.5–10000)] and ≥18 years [1340 (229–4360) vs. 3722 (555–10000)]. Dupilumab treatment reduced total serum IgE levels in patients aged 6 months and older with moderate-to-severe AD. Overall safety was consistent with the known dupilumab safety profile. [ABSTRACT FROM AUTHOR]

Background: Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies.Objective: We sought to evaluate dupilumab treatment on patient-reported outcomes in adults with moderate to severe AD.Methods: Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo. Patient-reported outcomes included pruritus numeric rating scale; patient-reported sleep item on Scoring AD scale; Patient-Oriented Eczema Measure; Hospital Anxiety and Depression Scale; Dermatology Life Quality Index; and 5-dimension 3-level EuroQol.Results: Dupilumab reduced peak itch at 16 weeks relative to placebo by 1.1 to 3.2 points on numeric rating scale (P < .0001 all doses, except 100 mg every 4 weeks P < .05); improved sleep and health-related quality of life on Dermatology Life Quality Index and 5-dimension 3-level EuroQol (P < .05 all doses, except 100 mg every 4 weeks); and reduced anxiety and depression symptoms (P < .05 all doses). Dupilumab's effects appeared early and achieved clinically relevant improvements without significant safety concerns.Limitations: There are potential cultural differences affecting patient-reported outcome responses. Outcomes were secondary or exploratory end points.Conclusion: Dupilumab produced early and sustained patient-reported and clinically relevant improvements in sleep, mental health, and health-related quality of life; the two 300-mg dose regimens resulted in greatest benefits. [ABSTRACT FROM AUTHOR]

Background: The impact of dupilumab, an anti-interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown.Objectives: To assess T-cell-dependent and T-cell-independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety.Methods: In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16.Results: In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P < .001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo.Limitation: Patients' prior vaccination status was not available before enrollment.Conclusion: Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile. [ABSTRACT FROM AUTHOR]