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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]

Background: Current treat‐to‐target recommendations for atopic dermatitis (AD) may not include high enough treatment targets and do not fully consider patient needs. Objective: To develop recommendations for optimized AD management, including disease severity assessments, treatment goals and targets, and guidance for treatment escalation/modification. Methods: An international group of expert dermatologists drafted a series of recommendations for AD management using insights from a global patient study and 87 expert dermatologists from 44 countries. Experts voted on recommendations using a modified eDelphi voting process. Results: The Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations establish a novel approach to AD management, incorporating shared decision‐making and a concept for minimal disease activity (MDA). Consensus (≥70% agreement) was reached for all recommendations in 1 round of voting; strong consensus (≥90% agreement) was reached for 30/34 recommendations. In the AHEAD approach, patients select their most troublesome AD feature(s); the clinician chooses a corresponding patient‐reported severity measure and objective severity measure. Treatment targets are chosen from a list of 'moderate' and 'optimal' targets, with achievement of 'optimal' targets defined as MDA. Conclusions: Patient and expert insights led to the development of AHEAD recommendations, which establish a novel approach to AD management. Patients were not involved in the eDelphi voting process used to generate consensus on each recommendation. However, patient perspectives were captured in a global, qualitative patient research study that was considered by the experts in their initial drafting of the recommendations. [ABSTRACT FROM AUTHOR]

There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence‐based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk‐of‐bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H1 and/ or H2‐antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state‐of‐the‐art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well‐designed, high‐quality interventional trials are needed to establish evidence‐based treatment guidelines for AU. [ABSTRACT FROM AUTHOR]

Background: Autoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years). Methods: Atopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases ("AD + Type 2"; asthma, allergic rhinitis, food allergy, n = 431) or "solely AD" (n = 115). Also, subjects without AD but with Type‐2 diseases ("atopic controls," n = 52) and non‐atopic "healthy controls" (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. Results: Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. "AD + Type 2" showed a higher prevalence (16.4%) than "solely AD" (9.6%). "Atopic controls" (9.6%) were comparable with "solely AD" patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with "AD + Type 2". AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets. Conclusions: Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration. [ABSTRACT FROM AUTHOR]

Background: With the current trend in healthcare moving towards a more value‐based approach, it is essential to understand what value encompasses. Objectives: To develop an actionable value‐based outcome set (VOS) for daily practice. Methods: A mixed method approach was used consisting of four phases. Formerly, a systematic review was conducted, providing an overview of all patient‐relevant outcomes defined in current literature. These 23 outcomes were then presented to a group of patients, using a modified nominal group technique (NGT), to establish whether these results represented all of their relevant outcomes. Subsequently, these outcomes were ranked according to importance by patients attending our academic specialized psoriasis clinic. A review of the literature was performed to assess which instruments were available and suitable to evaluate the outcomes in this VOS. Finally, a pilot feasibility test was performed amongst patients. Results: Of the 23 outcomes, two were omitted from the ranking exercise after the NGT. In the ranking exercise, 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2), and treatments varied from topicals to biologicals. The outcomes scored as most important were symptom control, treatment efficacy, confidence in care and control of disease. The least important outcomes were comorbidity control, productivity and cost of care. A significant difference was shown between the ranking of the outcomes (p < 0.001). In total, 12 instruments were selected, which are reported by both patient and provider, to measure the outcomes in this VOS. Median completion time for the patient part was 30 min (IQR 2.8). Conclusions: This VOS is a first proposal to evaluate psoriasis care in a value‐based manner. Measuring these outcomes can enable us to critically appraise and improve current care processes, within the reality of available resources, thereby increasing value for patients. [ABSTRACT FROM AUTHOR]