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INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patients quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD. METHODS: Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. RESULTS: Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 - 7.8 vs - 2.8; ADvocate2 - 7.3 vs - 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 - 7.43 vs - 1.51; ADvocate2 - 4.95 vs - 0.82) and PROMIS Depression (ADvocate1 - 7.42 vs - 2.46; ADvocate2 - 4.28 vs - 2.00). CONCLUSIONS: Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline. TRIAL REGISTRATION: ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Background: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16weeks compared to placebo. Objectives: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment. Methods: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep). Results: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders. Conclusions: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD. ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2). [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) has different clinical presentations, pathophysiology, comorbidity frequencies, and genetic profiles in adult-onset vs childhood-onset disease. Based on these differences, it is plausible that treatment response would also be different between adult- and childhood-onset AD. Lebrikizumab, a novel, high affinity monoclonal antibody, selectively targeting IL-13 with high affinity and slow dissociation rate, has been approved in the EU, UK, and Japan and is under investigation in the US and elsewhere for the treatment of moderate-to-severe AD. Objectives To evaluate the Week-16 efficacy of lebrikizumab monotherapy by age of AD onset in adults and adolescents with moderate-to-severe AD from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), identically-designed, randomized, double-blind, placebo-controlled phase 3 trials. Methods In ADvocate1 and ADvocate2, eligible patients were randomly allocated 2:1 to receive lebrikizumab 250 mg or placebo every 2 weeks. The date of AD onset was collected, and age of onset was calculated accordingly. Patients were stratified by age of AD-onset as ≤2, >2-to-<18, and ≥18 years. Efficacy was assessed at Week 16 with the proportion of patients with Investigator's Global Assessment score of 0 or 1 with ≥2-point improvement (IGA 0,1; the trials' primary endpoint); ≥75% (EASI 75) and ≥90% (EASI 90) improvement in the Eczema Area and Severity Index from baseline; ≥4-point Pruritus Numeric Rating Scale (NRS) improvement from baseline (with baseline score ≥4), and percentage change in total EASI from baseline. Data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders or set to baseline values. Data from patients who discontinued treatment for other reasons were set to missing and analyzed by multiple imputation. This was a post-hoc analysis conducted on the modified, pooled intent-to-treat population. Treatment-by-age subgroup interaction was assessed with logistic regression. Binary outcomes were analyzed by the Cochran-Mantel-Haenszel method, and continuous outcomes were analyzed with ANCOVA. Results At baseline, the numbers of patients treated with lebrikizumab and placebo, respectively, were 215 and 117 in the ≤2 years AD-onset subgroup, 178 and 103 in the >2-to-<18 years subgroup, and 171 and 67 in the ≥18 years subgroup. At baseline, the percentages of patients with ≥1 atopic comorbidity were 81% in the ≤2 years subgroup, 74% in the >2-to-<18 years subgroup, and 58% in the ≥18 years subgroup. At Week 16, treatment-by-age subgroup interactions were not significant at the 0.10 level for IGA 0,1; EASI 75; EASI 90; and Pruritus NRS 4-pt improvement. Within each subgroup, a higher proportion of lebrikizumab-treated compared with placebo-treated patients (p<0.001) achieved IGA 0,1 responses (≤2 years: 41% vs. 12%; >2-to-<18 years: 35% vs. 12%; ≥18 years: 38% vs. 12%), EASI 75 responses (≤2 years: 57% vs. 17%; >2-to-<18 years: 51% vs. 16%; ≥18 years: 58% vs. 20%), and EASI 90 responses (≤2 years: 38% vs. 10%; >2-to-<18 years: 32% vs. 9%; ≥18 years: 33% vs. 8%). Additionally, the least-squares mean percentage change from baseline in total EASI score for lebrikizumab and placebo, respectively, was -65% and -26% in the ≤2 years subgroup, -60% and -26% in the >2-to-<18 years subgroup, and -63% and -30% in the ≥18 years subgroup (p<0.001 for lebrikizumab vs. placebo in all subgroups). The proportion of lebrikizumab-treated patients who reported ≥4-point improvement in Pruritus NRS from baseline (baseline ≥4) was greater compared with placebo-treated patients ([N]; ≤2 years: 43% [201] vs. 11% [108]; >2-to-<18 years: 41% [161] vs. 14% [96]; ≥18 years: 45% [154] vs. 12% [60]; p<0.001). Conclusions Regardless of age of AD onset, lebrikizumab was associated with significant improvements in AD signs and symptoms compared with placebo over 16 weeks of treatment. [ABSTRACT FROM AUTHOR]

Introduction/Background Biologics and Janus kinase inhibitors (JAKi) are promising treatment options for patients with atopic dermatitis (AD)1; however, no studies, to our knowledge, have evaluated differences in characteristics of patients on these medications in a real-world setting. Objective This study sought to describe the demographics, clinical characteristics, treatment patterns, and disease severity and patient-reported outcome measures of adult patients with AD initiating either a biologic or JAKi in the prospective, non-interventional CorEvitas AD Registry. Methods This cross-sectional study included patients initiating either a biologic (dupilumab or tralokinumab) or JAKi (abrocitinib or upadacitinib) in the CorEvitas AD Registry between 7/21/2020 and 7/31/2023. Patient characteristics were summarized at initiation of therapy using descriptive statistics, overall and by prior experience with biologic/JAKi therapy and systemic therapy (any registry-eligible systemic medication). Additionally, exploratory multivariable modified-Poisson regression was used to identify factors associated with biologic vs. JAKi initiation. Variables were selected by first using bivariate regression, and covariates with p-values ≤0.15 were submitted to a backward selection process. Age, sex, and race were included in the final model for representation purposes. Results The study reported 1,958 initiations, with 1,604 biologic initiations and 354 JAKi initiations. The initiated medication was the first-line systemic among 86.4% of the biologic initiators and 40.7% of the JAKi initiators. Biologic initiators were slightly older than JAKi initiators (mean age 50.7 years, SD 18.5 vs. mean 47.9, SD 17.0 years), with no major differences in sex, race/ethnicity, education, or work status. Differences were seen in history of infections (32.7% in biologic initiators vs. 44.9% in JAKi initiators) and rosacea (12.1% biologics vs. 5.9% JAKi). Furthermore, biologic initiators had greater disease severity than JAKi initiators as measured by body surface area % involvement (mean 26.0, SD 20.2 vs. mean 18.3, SD 19.4), validated Investigator Global Assessment for AD (severe vIGA-AD™, 34.4% vs. 24.6%), Eczema Area and Severity Index (EASI, mean 14.5, SD 12.0 vs. mean 10.7, SD 11.1) and SCoring AD (SCORAD, mean 48.2, SD 19.8 vs. mean 42.2, SD 20.1). Patient-reported outcomes were similar between groups. In adjusted analyses, factors positively associated with JAKi initiation compared to biologics included living in the Midwest US (vs. Northeast US, RR: 1.50, 95% CI: 1.14, 1.97), worst skin pain in 24 hours (RR: 1.05, 95% CI: 1.02, 1.09), and prior use of 1 or 2+ systemic therapies (vs. none, RR: 4.30, 95% CI: 2.29, 8.07 and RR: 5.49, 95% CI: 3.06, 9.84, respectively). Factors positively associated with biologic initiation included having a history of cancer (RR: 0.33, 95% CI: 0.22, 0.49), moderate vIGA-AD™ (vs. clear, RR: 0.74, 95% CI: 0.56, 0.98), hand involvement (RR: 0.73, 95% CI: 0.62, 0.86), and worst itch in 24 hours (RR: 0.97, 95% CI: 0.94, 0.99). Conclusions In this real-world assessment, certain characteristics differed between adult patients with AD initiating either biologics which were most commonly first-line agents or JAKi (more likely used after other systemic agents), although some effect sizes were small and may not be clinically meaningful. Study limitations to consider include that characteristics associated with biologic or JAKi initiation may be influenced by timing of medication approval and availability. These foundational results highlight the importance of individualized patient assessment when deciding among different therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic dermatitis (AD). Rapid onset of action is important for AD treatments to improve quality of life and relieve suffering. Objectives: This subanalysis evaluated how quickly baricitinib 1-mg and 2-mg reduced itch and associated sleep disturbance during the first 7 days after treatment initiation in a phase 3, double-blind, placebo-controlled trial. Methods: Adult patients with AD were randomized 1:1:1 to placebo (N = 147), baricitinib 1 mg (N = 147) or baricitinib 2 mg (N = 146). Patients kept daily diaries, completing the Itch Numeric Rating Scale (NRS) (itch severity from 0 = no itch to 10 = worst itch imaginable) and the Atopic Dermatitis Sleep Scale (ADSS) to measure sleep disturbance (number of nighttime awakenings because of itch). Mixed model repeated measures analysis was used to analyze change from day 1 to day 7 values. Results: Patients receiving either dose of baricitinib had a 9.9% decrease in itch NRS scores from baseline to Day 2 vs 1.5% decrease for placebo (significant between-group least squares mean [LSM] difference: 8.3; 95% CI −12.66 to −3.89; P =.0002). Baricitinib 2 mg reduced nighttime awakenings due to itch (ADSS item 2) at day 2 by 25.2% vs 3.9% in the placebo group (between-group LSM difference: −21.4, P =.0025). Baricitinib 2 mg continued to demonstrate a statistically significant difference from placebo in sleep symptoms at day 7 (LSM difference −23.9; P =.001). Conclusions: Baricitinib 2-mg provided relief from itching and sleep disturbance in patients with AD, beginning the day after taking first dose. Clinical trials at www.clinicaltrials.gov: BREEZE-AD5 (NCT03435081) [ABSTRACT FROM AUTHOR]

Background: The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex., Objectives: To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics., Methods: Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD ™ ; body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups., Results: Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment., Conclusion: While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.